chr17-28491461-C-T

Variant names:

• chr17-28491461-C-T
• rs200761343
• NM_003984.4:c.599C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003984.4(SLC13A2):​c.599C>T​(p.Thr200Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000068 (0 hom.)
• Consequence: SLC13A2 NM_003984.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.116
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012827992).

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.599C>T	p.Thr200Met	missense	Exon 5 of 12	NP_003975.1	Q13183-1
	SLC13A2	NM_001145975.2		c.746C>T	p.Thr249Met	missense	Exon 5 of 12	NP_001139447.1	Q13183-3
	SLC13A2	NM_001346683.2		c.467C>T	p.Thr156Met	missense	Exon 6 of 13	NP_001333612.1	J3QL78

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	ENST00000314669.10	TSL:1 MANE Select	c.599C>T	p.Thr200Met	missense	Exon 5 of 12	ENSP00000316202.6	Q13183-1
	RSKR	ENST00000481916.6	TSL:1	n.*1196-35352G>A		intron	N/A	ENSP00000436369.2	Q96LW2-2
	SLC13A2	ENST00000855217.1		c.746C>T	p.Thr249Met	missense	Exon 5 of 12	ENSP00000525276.1

Frequencies

GnomAD3 genomes AF: 0.0000525 AC: 8 AN: 152250 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000120 AC: 30 AN: 250828 AF XY: 0.000118

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00153

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000684 AC: 100 AN: 1461342 Hom.: 0 Cov.: 31 AF XY: 0.0000564 AC XY: 41 AN XY: 726998

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00196 AC: 78 AN: 39700

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111994

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152368 Hom.: 0 Cov.: 33 AF XY: 0.0000671 AC XY: 5 AN XY: 74512

African (AFR) AF: 0.00 AC: 0 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000272 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.000123 AC: 15

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.3
DANN	Benign	0.94
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.12
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.098
Sift	Benign	0.066	T
Sift4G	Benign	0.10	T
Polyphen		0.016	B
Vest4		0.17
MVP		0.26
MPC		0.49
ClinPred		0.015	T
GERP RS		-0.74
Varity_R		0.019
gMVP		0.48
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs200761343; hg19: chr17-26818479; COSMIC: COSV58993492;