6-25917006-C-T

Position:

• chr6-25917006-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001286123.3(SLC17A2):​c.731G>A​(p.Arg244Lys) 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. 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)
• Consequence: SLC17A2 NM_001286123.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.286

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08095974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A2	NM_001286123.3	c.731G>A	p.Arg244Lys	missense_variant	7/12	ENST00000377850.8	NP_001273052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A2	ENST00000377850.8	c.731G>A	p.Arg244Lys	missense_variant	7/12	5	NM_001286123.3	ENSP00000367081	P1
SLC17A2	ENST00000360488.7	c.731G>A	p.Arg244Lys	missense_variant	7/11	1		ENSP00000353677
SLC17A2	ENST00000265425.3	c.731G>A	p.Arg244Lys	missense_variant	6/11	5		ENSP00000265425

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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

Aug 08, 2022

The c.731G>A (p.R244K) alteration is located in exon 7 (coding exon 6) of the SLC17A2 gene. This alteration results from a G to A substitution at nucleotide position 731, causing the arginine (R) at amino acid position 244 to be replaced by a lysine (K). 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	0.080
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.23
DANN	Benign	0.74
DEOGEN2	Benign	0.11	.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.026	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.081	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.10	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.26	N;N;N
REVEL	Benign	0.049
Sift	Benign	0.63	T;T;T
Sift4G	Benign	0.75	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.090
MutPred		0.45		Gain of ubiquitination at R244 (P = 0.009);Gain of ubiquitination at R244 (P = 0.009);Gain of ubiquitination at R244 (P = 0.009);
MVP		0.072
MPC		0.22
ClinPred		0.021	T
GERP RS		-0.26
Varity_R		0.042
gMVP		0.093

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs767201040; hg19: chr6-25917234;