6-73644452-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012434.5(SLC17A5):c.246G>A(p.Ala82Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.082 in 1,613,430 control chromosomes in the GnomAD database, including 6,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1063 hom., cov: 33)

Exomes 𝑓: 0.079 ( 5427 hom. )

Consequence

SLC17A5
NM_012434.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.753

Publications

20 publications found

Variant links:

Genes affected

SLC17A5 (HGNC:10933): (solute carrier family 17 member 5) This gene encodes a membrane transporter that exports free sialic acids that have been cleaved off of cell surface lipids and proteins from lysosomes. Mutations in this gene cause sialic acid storage diseases, including infantile sialic acid storage disorder and and Salla disease, an adult form. [provided by RefSeq, Jul 2008]

SLC17A5 Gene-Disease associations (from GenCC):

free sialic acid storage disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Salla disease
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, Myriad Women’s Health
free sialic acid storage disease, infantile form
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
intermediate severe Salla disease
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC17A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-73644452-C-T is Benign according to our data. Variant chr6-73644452-C-T is described in ClinVar as Benign. ClinVar VariationId is 130316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.753 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A5	NM_012434.5 link	c.246G>A	p.Ala82Ala	synonymous_variant	Exon 2 of 11	ENST00000355773.6	NP_036566.1	Q9NRA2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A5	ENST00000355773.6 link	c.246G>A	p.Ala82Ala	synonymous_variant	Exon 2 of 11	1	NM_012434.5	ENSP00000348019.5		Q9NRA2-1
SLC17A5	ENST00000481996.1 link	n.12G>A		non_coding_transcript_exon_variant	Exon 1 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.107

AC:

16303

AN:

152026

Hom.:

1062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.0959

Gnomad FIN

AF:

0.0484

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.0730

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.0988

AC:

24837

AN:

251362

AF XY:

0.0962

show subpopulations

Gnomad AFR exome

AF:

0.150

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.155

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.0488

Gnomad NFE exome

AF:

0.0732

Gnomad OTH exome

AF:

0.114

GnomAD4 exome

AF:

0.0793

AC:

115919

AN:

1461286

Hom.:

5427

Cov.:

AF XY:

0.0798

AC XY:

58003

AN XY:

727000

show subpopulations

African (AFR)

AF:

0.156

AC:

5219

AN:

33458

American (AMR)

AF:

0.132

AC:

5922

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

4101

AN:

26120

East Asian (EAS)

AF:

0.176

AC:

6980

AN:

39674

South Asian (SAS)

AF:

0.103

AC:

8908

AN:

86228

European-Finnish (FIN)

AF:

0.0504

AC:

2690

AN:

53410

Middle Eastern (MID)

AF:

0.180

AC:

1039

AN:

5766

European-Non Finnish (NFE)

AF:

0.0676

AC:

75137

AN:

1111540

Other (OTH)

AF:

0.0981

AC:

5923

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4874

9748

14621

19495

24369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2978

5956

8934

11912

14890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.107

AC:

16324

AN:

152144

Hom.:

1063

Cov.:

AF XY:

0.107

AC XY:

7931

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.154

AC:

6393

AN:

41478

American (AMR)

AF:

0.143

AC:

2191

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.157

AC:

544

AN:

3470

East Asian (EAS)

AF:

0.171

AC:

884

AN:

5174

South Asian (SAS)

AF:

0.0966

AC:

466

AN:

4824

European-Finnish (FIN)

AF:

0.0484

AC:

513

AN:

10596

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0730

AC:

4965

AN:

68010

Other (OTH)

AF:

0.135

AC:

285

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

742

1484

2225

2967

3709

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0898

Hom.:

2497

Bravo

AF:

0.117

Asia WGS

AF:

0.143

AC:

497

AN:

3478

EpiCase

AF:

0.0832

EpiControl

AF:

0.0836

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Dec 11, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 09, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Salla disease

Benign:4

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sialic acid storage disease, severe infantile type

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:2

Feb 08, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The SLC17A5 c.246G>A (p.Ala82Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a polymorphism outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 11883/121310 control chromosomes (671 homozygotes) at a frequency of 0.0979557, which is approximately 41 times the estimated maximal expected allele frequency of a pathogenic SLC17A5 variant (0.0023717), strong evidence that this variant is a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Due to the synonymous nature of the variant, the lack of predicted effect on splicing and the high frequency in the contol population, this variant is classified as benign. -

Apr 19, 2017

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.48

PhyloP100

0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over