rs201284672

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 16 ACMG points: 16P and 0B. PVS1PP5_Very_Strong

The NM_012434.5(SLC17A5):c.918T>G(p.Tyr306*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00007 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

SLC17A5
NM_012434.5 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, multiple submitters, no conflicts P:13

Conservation

PhyloP100: 0.747

Publications

5 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: Myriad Women’s Health, G2P, PanelApp Australia, Orphanet, Genomics England PanelApp
free sialic acid storage disease, infantile form
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, 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: Pathogenic. The variant received 16 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 6-73621864-A-C is Pathogenic according to our data. Variant chr6-73621864-A-C is described in ClinVar as Pathogenic. ClinVar VariationId is 440272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012434.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A5	NM_012434.5	MANE Select	c.918T>G	p.Tyr306*	stop_gained	Exon 7 of 11	NP_036566.1	Q9NRA2-1
SLC17A5	NM_001382633.1		c.918T>G	p.Tyr306*	stop_gained	Exon 7 of 12	NP_001369562.1
SLC17A5	NM_001382631.1		c.939T>G	p.Tyr313*	stop_gained	Exon 8 of 12	NP_001369560.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A5	ENST00000355773.6	TSL:1 MANE Select	c.918T>G	p.Tyr306*	stop_gained	Exon 7 of 11	ENSP00000348019.5	Q9NRA2-1
SLC17A5	ENST00000957536.1		c.1032T>G	p.Tyr344*	stop_gained	Exon 8 of 12	ENSP00000627595.1
SLC17A5	ENST00000957535.1		c.840T>G	p.Tyr280*	stop_gained	Exon 7 of 11	ENSP00000627594.1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000835

AC:

AN:

251364

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000463

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000630

AC:

AN:

1461234

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.000470

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39650

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000603

AC:

AN:

1111474

Other (OTH)

AF:

0.0000663

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000138

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41592

American (AMR)

AF:

0.00105

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000976

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Salla disease (6)

not provided (3)

Sialic acid storage disease, severe infantile type (2)

not specified (1)

Sialic acid storage disease, severe infantile type;C1096903:Salla disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.40

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.84

PhyloP100

0.75

Vest4

0.91

GERP RS

2.3

Mutation Taster

=22/178

disease causing (ClinVar)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over