17-28490472-A-G

Variant names:

• chr17-28490472-A-G
• rs2068984093
• NM_003984.4:c.250A>G

Variant summary

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

The NM_003984.4(SLC13A2):​c.250A>G​(p.Lys84Glu) variant causes a missense change. 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: 5.19

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 rank	MANE	Protein	UniProt
SLC13A2	NM_003984.4	c.250A>G	p.Lys84Glu	missense_variant	Exon 3 of 12	ENST00000314669.10	NP_003975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC13A2	ENST00000314669.10	c.250A>G	p.Lys84Glu	missense_variant	Exon 3 of 12	1	NM_003984.4	ENSP00000316202.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.397A>G (p.K133E) alteration is located in exon 3 (coding exon 3) of the SLC13A2 gene. This alteration results from a A to G substitution at nucleotide position 397, causing the lysine (K) at amino acid position 133 to be replaced by a glutamic acid (E). 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	0.24
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.21	.;T;T
Eigen	Benign	0.077
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.1	.;M;.
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.0	D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.029	D;T;.
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.98	.;D;.
Vest4		0.48
MutPred		0.53		.;Loss of ubiquitination at K84 (P = 0.021);.;
MVP		0.38
MPC		0.91
ClinPred		0.97	D
GERP RS		3.2
Varity_R		0.16
gMVP		0.69

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: rs2068984093; hg19: chr17-26817490;