6-25913336-C-T

Variant summary

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

The NM_001286123.3(SLC17A2):​c.1418G>A​(p.Arg473Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/17 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)

Consequence

SLC17A2
NM_001286123.3 missense

Scores

1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0470
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]

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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=0.044036508).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC17A2NM_001286123.3 linkc.1418G>A p.Arg473Lys missense_variant Exon 12 of 12 ENST00000377850.8 NP_001273052.1 O00624-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC17A2ENST00000377850.8 linkc.1418G>A p.Arg473Lys missense_variant Exon 12 of 12 5 NM_001286123.3 ENSP00000367081.3 O00624-3
SLC17A2ENST00000360488.7 linkc.1270G>A p.Gly424Arg missense_variant Exon 11 of 11 1 ENSP00000353677.3 O00624-2
SLC17A2ENST00000265425 linkc.*133G>A 3_prime_UTR_variant Exon 11 of 11 5 ENSP00000265425.3 O00624-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1270G>A (p.G424R) alteration is located in exon 11 (coding exon 10) of the SLC17A2 gene. This alteration results from a G to A substitution at nucleotide position 1270, causing the glycine (G) at amino acid position 424 to be replaced by an arginine (R). 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
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
9.4
DANN
Benign
0.78
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.049
N
LIST_S2
Benign
0.46
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.044
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.24
T
PROVEAN
Uncertain
-4.3
D
REVEL
Benign
0.056
Sift
Benign
0.099
T
Sift4G
Benign
0.22
T
Polyphen
0.0010
B
Vest4
0.16
MutPred
0.44
Loss of ubiquitination at K422 (P = 0.0437);
MVP
0.067
MPC
0.25
ClinPred
0.37
T
GERP RS
0.57

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs531959222; hg19: chr6-25913564; API