6-25913336-C-T

Variant names:

• chr6-25913336-C-T
• rs531959222
• NM_001286123.3:c.1418G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0470

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]

ACMG classification

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
SLC17A2	NM_001286123.3	c.1418G>A	p.Arg473Lys	missense_variant	Exon 12 of 12	ENST00000377850.8	NP_001273052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A2	ENST00000377850.8	c.1418G>A	p.Arg473Lys	missense_variant	Exon 12 of 12	5	NM_001286123.3	ENSP00000367081.3
SLC17A2	ENST00000360488.7	c.1270G>A	p.Gly424Arg	missense_variant	Exon 11 of 11	1		ENSP00000353677.3
SLC17A2	ENST00000265425	c.*133G>A		3_prime_UTR_variant	Exon 11 of 11	5		ENSP00000265425.3

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

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

Other links and lift over

dbSNP: rs531959222; hg19: chr6-25913564;