rs11568476

Variant names:

• chr17-28495775-G-A
• rs11568476
• NM_003984.4:c.1429G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-28495775-G-A
• chr17-28495775-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001145975.2(SLC13A2):​c.1576G>A​(p.Val526Met) variant causes a missense change. The variant allele was found at a frequency of 0.0025 in 1,613,306 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0019 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (10 hom.)
• Consequence: SLC13A2 NM_001145975.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.02229023).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145975.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	NM_003984.4	MANE Select	c.1429G>A	p.Val477Met	missense	Exon 10 of 12	NP_003975.1
	SLC13A2	NM_001145975.2		c.1576G>A	p.Val526Met	missense	Exon 10 of 12	NP_001139447.1
	SLC13A2	NM_001346683.2		c.1297G>A	p.Val433Met	missense	Exon 11 of 13	NP_001333612.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	ENST00000314669.10	TSL:1 MANE Select	c.1429G>A	p.Val477Met	missense	Exon 10 of 12	ENSP00000316202.6
	RSKR	ENST00000481916.6	TSL:1	n.*1196-39666C>T		intron	N/A	ENSP00000436369.2
	SLC13A2	ENST00000855217.1		c.1579G>A	p.Val527Met	missense	Exon 10 of 12	ENSP00000525276.1

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 281 AN: 152028 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.00192

GnomAD2 exomes AF: 0.00179 AC: 448 AN: 250760 AF XY: 0.00172

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00348

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000946

Gnomad NFE exome AF: 0.00249

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00257 AC: 3756 AN: 1461160 Hom.: 10 Cov.: 31 AF XY: 0.00254 AC XY: 1844 AN XY: 726912

African (AFR) AF: 0.000687 AC: 23 AN: 33478

American (AMR) AF: 0.00405 AC: 181 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0000765 AC: 2 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000429 AC: 37 AN: 86228

European-Finnish (FIN) AF: 0.000132 AC: 7 AN: 52840

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.00302 AC: 3353 AN: 1111930

Other (OTH) AF: 0.00237 AC: 143 AN: 60380

GnomAD4 genome AF: 0.00185 AC: 282 AN: 152146 Hom.: 2 Cov.: 32 AF XY: 0.00186 AC XY: 138 AN XY: 74386

African (AFR) AF: 0.000651 AC: 27 AN: 41506

American (AMR) AF: 0.00288 AC: 44 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00296 AC: 201 AN: 67970

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00231 Hom.: 2

Bravo AF: 0.00199

TwinsUK AF: 0.00162 AC: 6

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00157 AC: 191

EpiCase AF: 0.00278

EpiControl AF: 0.00415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		4.6
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.20
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.042	D
Polyphen		1.0	D
Vest4		0.62
MVP		0.34
MPC		0.93
ClinPred		0.10	T
GERP RS		5.3
Varity_R		0.45
gMVP		0.75
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs11568476; hg19: chr17-26822793; COSMIC: COSV58998618; COSMIC: COSV58998618;