17-28497138-A-G

Position:

• chr17-28497138-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003984.4(SLC13A2):​c.1648A>G​(p.Ile550Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 1,613,718 control chromosomes in the GnomAD database, including 120,054 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.43 (15272 hom., cov: 32)
  • Exomes 𝑓: 0.37 (104782 hom.)
• Consequence: SLC13A2 NM_003984.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454

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]

SLC13A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.599328E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC13A2	NM_003984.4	c.1648A>G	p.Ile550Val	missense_variant	12/12	ENST00000314669.10	NP_003975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC13A2	ENST00000314669.10	c.1648A>G	p.Ile550Val	missense_variant	12/12	1	NM_003984.4	ENSP00000316202.6

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65976 AN: 151796 Hom.: 15223 Cov.: 32

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.425

GnomAD3 exomes AF: 0.405 AC: 101654 AN: 251160 Hom.: 21544 AF XY: 0.397 AC XY: 53872 AN XY: 135740

Gnomad AFR exome AF: 0.598

Gnomad AMR exome AF: 0.527

Gnomad ASJ exome AF: 0.371

Gnomad EAS exome AF: 0.363

Gnomad SAS exome AF: 0.442

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.349

Gnomad OTH exome AF: 0.390

GnomAD4 exome AF: 0.374 AC: 546171 AN: 1461804 Hom.: 104782 Cov.: 51 AF XY: 0.374 AC XY: 271771 AN XY: 727212

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.521

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.408

Gnomad4 SAS exome AF: 0.440

Gnomad4 FIN exome AF: 0.363

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.388

GnomAD4 genome AF: 0.435 AC: 66075 AN: 151914 Hom.: 15272 Cov.: 32 AF XY: 0.434 AC XY: 32217 AN XY: 74272

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.440

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.428

Alfa AF: 0.371 Hom.: 24514

Bravo AF: 0.448

TwinsUK AF: 0.351 AC: 1303

ALSPAC AF: 0.360 AC: 1387

ESP6500AA AF: 0.579 AC: 2552

ESP6500EA AF: 0.346 AC: 2975

ExAC AF: 0.404 AC: 49035

Asia WGS AF: 0.416 AC: 1446 AN: 3478

EpiCase AF: 0.352

EpiControl AF: 0.349

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.65
DEOGEN2	Benign	0.031	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.37	T;T
MetaRNN	Benign	0.0000056	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	.;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.31	N;N
REVEL	Benign	0.027
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0	.;B
Vest4		0.023
MPC		0.23
ClinPred		0.0027	T
GERP RS		3.2
Varity_R		0.058
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs11567842; hg19: chr17-26824156; COSMIC: COSV58993870; COSMIC: COSV58993870;