NM_003984.4:c.928G>C

Variant names:

• chr17-28493620-G-C
• rs11568441
• NM_003984.4:c.928G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_003984.4(SLC13A2):​c.928G>C​(p.Ala310Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,612,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: SLC13A2 NM_003984.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.92
• Publications: 4 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08720422).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	NM_003984.4	MANE Select	c.928G>C	p.Ala310Pro	missense	Exon 7 of 12	NP_003975.1
	SLC13A2	NM_001145975.2		c.1075G>C	p.Ala359Pro	missense	Exon 7 of 12	NP_001139447.1
	SLC13A2	NM_001346683.2		c.796G>C	p.Ala266Pro	missense	Exon 8 of 13	NP_001333612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC13A2	ENST00000314669.10	TSL:1 MANE Select	c.928G>C	p.Ala310Pro	missense	Exon 7 of 12	ENSP00000316202.6
	RSKR	ENST00000481916.6	TSL:1	n.*1196-37511C>G		intron	N/A	ENSP00000436369.2
	SLC13A2	ENST00000444914.7	TSL:2	c.1075G>C	p.Ala359Pro	missense	Exon 7 of 12	ENSP00000392411.3

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152226 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000147 AC: 37 AN: 250870 AF XY: 0.000140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1460196 Hom.: 0 Cov.: 31 AF XY: 0.000116 AC XY: 84 AN XY: 726024

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.000560 AC: 25 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1110692

Other (OTH) AF: 0.000182 AC: 11 AN: 60330

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.000654 AC: 10 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000565 Hom.: 0

Bravo AF: 0.000140

ExAC AF: 0.000115 AC: 14

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		2.9
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.098
Sift	Benign	0.066	T
Sift4G	Benign	0.086	T
Polyphen		0.054	B
Vest4		0.50
MVP		0.048
MPC		1.0
ClinPred		0.21	T
GERP RS		3.5
Varity_R		0.71
gMVP		0.83
Mutation Taster		=79/21	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: rs11568441; hg19: chr17-26820638;