17-28494099-G-T

Variant summary

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

The NM_003984.4(SLC13A2):c.1180G>T(p.Asp394Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC13A2 NM_003984.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.51

Genes affected

SLC13A2 (HGNC:10917): (solute carrier family 13 member 2) The protein encoded by this gene is a sodium-coupled citrate transporter that is regulated by the chaperone activity of cyclophilin b. The encoded protein may play a role in the formation of kidney stones. [provided by RefSeq, Oct 2016]

RSKR (HGNC:26314): (ribosomal protein S6 kinase related) Predicted to enable protein kinase activity. Predicted to be involved in protein phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC13A2	NM_003984.4	c.1180G>T	p.Asp394Tyr	missense_variant	8/12	ENST00000314669.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC13A2	ENST00000314669.10	c.1180G>T	p.Asp394Tyr	missense_variant	8/12	1	NM_003984.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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

Oct 26, 2021

The c.1327G>T (p.D443Y) alteration is located in exon 8 (coding exon 8) of the SLC13A2 gene. This alteration results from a G to T substitution at nucleotide position 1327, causing the aspartic acid (D) at amino acid position 443 to be replaced by a tyrosine (Y). 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	0.082
BayesDel_addAF	Benign	-0.0061	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	21
Dann	Uncertain	0.99
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.67	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.34	T
MutationTaster	Benign	0.94	D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.030	D;D
Polyphen		0.91	.;P
Vest4		0.35
MutPred		0.77		.;Loss of disorder (P = 0.0341);
MVP		0.42
MPC		0.95
ClinPred		0.97	D
GERP RS		0.17
Varity_R		0.18
gMVP		0.75

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: chr17-26821117; COSMIC: COSV105903226; COSMIC: COSV105903226;