Genetic Variant SLC17A2:p.Trp287Ser (chr6-25916755-C-G) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001286123.3(SLC17A2):c.860G>C(p.Trp287Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W287L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC17A2
NM_001286123.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69

Publications

1 publications found

Variant links:

Genes affected

SLC17A2 (HGNC:10930): (solute carrier family 17 member 2) Predicted to enable sialic acid transmembrane transporter activity. Predicted to be involved in sialic acid transport. Predicted to be located in membrane. Predicted to be active in lysosome. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.953

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286123.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A2	NM_001286123.3	MANE Select	c.860G>C	p.Trp287Ser	missense	Exon 8 of 12	NP_001273052.1	O00624-3
SLC17A2	NM_005835.4		c.860G>C	p.Trp287Ser	missense	Exon 8 of 11	NP_005826.1	O00624-2
SLC17A2	NM_001286125.2		c.860G>C	p.Trp287Ser	missense	Exon 7 of 10	NP_001273054.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A2	ENST00000377850.8	TSL:5 MANE Select	c.860G>C	p.Trp287Ser	missense	Exon 8 of 12	ENSP00000367081.3	O00624-3
SLC17A2	ENST00000360488.7	TSL:1	c.860G>C	p.Trp287Ser	missense	Exon 8 of 11	ENSP00000353677.3	O00624-2
SLC17A2	ENST00000882944.1		c.860G>C	p.Trp287Ser	missense	Exon 8 of 13	ENSP00000553003.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251472

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111870

Other (OTH)

AF:

0.00

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

Eigen

Pathogenic

0.91

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.73

M_CAP

Benign

0.040

MetaRNN

Pathogenic

0.95

MetaSVM

Uncertain

0.097

MutationAssessor

Pathogenic

3.2

PhyloP100

5.7

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-13

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.73

MutPred

0.82

Loss of stability (P = 0.1613)

MVP

0.77

MPC

1.0

ClinPred

1.0

GERP RS

4.7

Varity_R

0.82

gMVP

0.88

Mutation Taster

=60/40

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over