rs16883930

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012434.5(SLC17A5):c.886G>A(p.Val296Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0117 in 1,613,866 control chromosomes in the GnomAD database, including 463 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 57 hom., cov: 33)

Exomes 𝑓: 0.011 ( 406 hom. )

Consequence

SLC17A5
NM_012434.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.70

Publications

15 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022813678).

BP6

Variant 6-73621896-C-T is Benign according to our data. Variant chr6-73621896-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 198552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A5	NM_012434.5 link	c.886G>A	p.Val296Ile	missense_variant	Exon 7 of 11	ENST00000355773.6	NP_036566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A5	ENST00000355773.6 link	c.886G>A	p.Val296Ile	missense_variant	Exon 7 of 11	1	NM_012434.5	ENSP00000348019.5

Frequencies

GnomAD3 genomes

AF:

0.0150

AC:

2279

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0415

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.0176

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00628

Gnomad OTH

AF:

0.0292

GnomAD2 exomes

AF:

0.0236

AC:

5939

AN:

251438

AF XY:

0.0214

show subpopulations

Gnomad AFR exome

AF:

0.00615

Gnomad AMR exome

AF:

0.0554

Gnomad ASJ exome

AF:

0.0206

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0131

Gnomad NFE exome

AF:

0.00627

Gnomad OTH exome

AF:

0.0254

GnomAD4 exome

AF:

0.0114

AC:

16613

AN:

1461602

Hom.:

406

Cov.:

AF XY:

0.0112

AC XY:

8111

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00633

AC:

212

AN:

33474

American (AMR)

AF:

0.0543

AC:

2429

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0218

AC:

569

AN:

26128

East Asian (EAS)

AF:

0.0993

AC:

3939

AN:

39656

South Asian (SAS)

AF:

0.0186

AC:

1608

AN:

86252

European-Finnish (FIN)

AF:

0.0119

AC:

633

AN:

53416

Middle Eastern (MID)

AF:

0.0397

AC:

229

AN:

5764

European-Non Finnish (NFE)

AF:

0.00523

AC:

5815

AN:

1111814

Other (OTH)

AF:

0.0195

AC:

1179

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

866

1732

2597

3463

4329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.0150

AC:

2281

AN:

152264

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1180

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00719

AC:

299

AN:

41568

American (AMR)

AF:

0.0416

AC:

635

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3472

East Asian (EAS)

AF:

0.109

AC:

565

AN:

5182

South Asian (SAS)

AF:

0.0176

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0128

AC:

136

AN:

10600

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00628

AC:

427

AN:

68012

Other (OTH)

AF:

0.0293

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

109

219

328

438

547

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0114

Hom.:

153

Bravo

AF:

0.0176

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.0221

AC:

2682

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

EpiCase

AF:

0.00747

EpiControl

AF:

0.00747

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

May 31, 2018

SIB Swiss Institute of Bioinformatics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -

Oct 14, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 12, 2016

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. -

Salla disease

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sialic acid storage disease, severe infantile type

Benign:1

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.17

Eigen

Benign

0.095

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

PhyloP100

5.7

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.41

REVEL

Benign

0.20

Sift

Benign

0.38

Sift4G

Benign

0.58

Polyphen

0.58

Vest4

0.14

MPC

0.16

ClinPred

0.017

GERP RS

5.9

Varity_R

0.13

gMVP

0.26

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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