17-28497138-A-G

Variant names:

• chr17-28497138-A-G
• rs11567842
• NM_003984.4:c.1648A>G

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 38 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003984.4. 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.1648A>G	p.Ile550Val	missense	Exon 12 of 12	NP_003975.1
	SLC13A2	NM_001145975.2		c.1795A>G	p.Ile599Val	missense	Exon 12 of 12	NP_001139447.1
	SLC13A2	NM_001346683.2		c.1516A>G	p.Ile506Val	missense	Exon 13 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.1648A>G	p.Ile550Val	missense	Exon 12 of 12	ENSP00000316202.6
	RSKR	ENST00000481916.6	TSL:1	n.*1196-41029T>C		intron	N/A	ENSP00000436369.2
	SLC13A2	ENST00000855217.1		c.1798A>G	p.Ile600Val	missense	Exon 12 of 12	ENSP00000525276.1

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

GnomAD2 exomes AF: 0.405 AC: 101654 AN: 251160 AF XY: 0.397

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 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

African (AFR) AF: 0.600 AC: 20089 AN: 33478

American (AMR) AF: 0.521 AC: 23289 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 9785 AN: 26130

East Asian (EAS) AF: 0.408 AC: 16209 AN: 39700

South Asian (SAS) AF: 0.440 AC: 37912 AN: 86254

European-Finnish (FIN) AF: 0.363 AC: 19375 AN: 53412

Middle Eastern (MID) AF: 0.459 AC: 2645 AN: 5768

European-Non Finnish (NFE) AF: 0.354 AC: 393437 AN: 1111952

Other (OTH) AF: 0.388 AC: 23430 AN: 60392

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

African (AFR) AF: 0.594 AC: 24574 AN: 41390

American (AMR) AF: 0.480 AC: 7330 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.378 AC: 1311 AN: 3466

East Asian (EAS) AF: 0.370 AC: 1906 AN: 5148

South Asian (SAS) AF: 0.440 AC: 2116 AN: 4812

European-Finnish (FIN) AF: 0.363 AC: 3845 AN: 10586

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23668 AN: 67928

Other (OTH) AF: 0.428 AC: 903 AN: 2108

Alfa AF: 0.383 Hom.: 38918

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 v4.9

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
MetaRNN	Benign	0.0000056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.45
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	1.0	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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11567842; hg19: chr17-26824156; COSMIC: COSV58993870; COSMIC: COSV58993870;