Variant 6-25923871-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001286123.3(SLC17A2):c.64C>G(p.Leu22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC17A2
NM_001286123.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.77

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047884107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A2	NM_001286123.3 linkuse as main transcript	c.64C>G	p.Leu22Val	missense_variant	3/12	ENST00000377850.8	NP_001273052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A2	ENST00000377850.8 linkuse as main transcript	c.64C>G	p.Leu22Val	missense_variant	3/12	5	NM_001286123.3	ENSP00000367081	P1	O00624-3
SLC17A2	ENST00000360488.7 linkuse as main transcript	c.64C>G	p.Leu22Val	missense_variant	3/11	1		ENSP00000353677		O00624-2
SLC17A2	ENST00000265425.3 linkuse as main transcript	c.64C>G	p.Leu22Val	missense_variant	2/11	5		ENSP00000265425		O00624-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 05, 2023

The c.64C>G (p.L22V) alteration is located in exon 3 (coding exon 2) of the SLC17A2 gene. This alteration results from a C to G substitution at nucleotide position 64, causing the leucine (L) at amino acid position 22 to be replaced by a valine (V). 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

Benign

0.074

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

3.4

DANN

Benign

0.95

DEOGEN2

Benign

0.065

.;.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0064

MetaRNN

Benign

0.048

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L

MutationTaster

Benign

0.93

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.30

T;T;T

Sift4G

Benign

0.44

T;T;T

Polyphen

0.0090

B;.;B

Vest4

0.20

MutPred

0.53

Gain of catalytic residue at L22 (P = 0.0772);Gain of catalytic residue at L22 (P = 0.0772);Gain of catalytic residue at L22 (P = 0.0772);

MVP

0.081

MPC

0.22

ClinPred

0.035

GERP RS

-1.5

Varity_R

0.076

gMVP

0.27

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

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