6-25913393-C-T

Position:

• chr6-25913393-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001286123.3(SLC17A2):​c.1361G>A​(p.Gly454Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 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: 3.67

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27170575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A2	NM_001286123.3	c.1361G>A	p.Gly454Asp	missense_variant	12/12	ENST00000377850.8	NP_001273052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A2	ENST00000377850.8	c.1361G>A	p.Gly454Asp	missense_variant	12/12	5	NM_001286123.3	ENSP00000367081.3
SLC17A2	ENST00000360488.7	c.1213G>A	p.Ala405Thr	missense_variant	11/11	1		ENSP00000353677.3
SLC17A2	ENST00000265425.3	c.*76G>A		3_prime_UTR_variant	11/11	5		ENSP00000265425.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

The c.1213G>A (p.A405T) 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 1213, causing the alanine (A) at amino acid position 405 to be replaced by a threonine (T). 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	-0.20	T
BayesDel_noAF	Benign	-0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-0.40	T
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.76	N
REVEL	Benign	0.25
Sift	Benign	0.15	T
Sift4G	Benign	0.25	T
Polyphen		0.45	B
Vest4		0.14
MutPred		0.65		Loss of helix (P = 0.0167);
MVP		0.55
MPC		0.73
ClinPred		0.99	D
GERP RS		4.7

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.

Other links and lift over

hg19: chr6-25913621;