Genetic Variant NM_001286123.3:c.496T>C (chr6-25921072-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001286123.3(SLC17A2):c.496T>C(p.Phe166Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC17A2
NM_001286123.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.445

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A2	NM_001286123.3 link	c.496T>C	p.Phe166Leu	missense_variant	Exon 5 of 12	ENST00000377850.8	NP_001273052.1	O00624-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC17A2	ENST00000377850.8 link	c.496T>C	p.Phe166Leu	missense_variant	Exon 5 of 12	5	NM_001286123.3	ENSP00000367081.3	O00624-3
SLC17A2	ENST00000360488.7 link	c.496T>C	p.Phe166Leu	missense_variant	Exon 5 of 11	1		ENSP00000353677.3	O00624-2
SLC17A2	ENST00000265425.3 link	c.496T>C	p.Phe166Leu	missense_variant	Exon 4 of 11	5		ENSP00000265425.3	O00624-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.496T>C (p.F166L) alteration is located in exon 5 (coding exon 4) of the SLC17A2 gene. This alteration results from a T to C substitution at nucleotide position 496, causing the phenylalanine (F) at amino acid position 166 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

.;.;T

Eigen

Benign

0.076

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.44

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-4.5

D;D;D

REVEL

Benign

0.19

Sift

Benign

0.070

T;T;T

Sift4G

Benign

0.46

T;T;T

Polyphen

0.73

P;.;P

Vest4

0.62

MutPred

0.61

Loss of catalytic residue at F166 (P = 0.0296);Loss of catalytic residue at F166 (P = 0.0296);Loss of catalytic residue at F166 (P = 0.0296);

MVP

0.27

MPC

0.38

ClinPred

0.92

GERP RS

3.7

Varity_R

0.25

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over