17-28489241-C-T

Variant names:

• chr17-28489241-C-T
• rs45443898
• NM_003984.4:c.130C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003984.4(SLC13A2):​c.130C>T​(p.Leu44Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000989 in 1,614,030 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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 0.00083 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (28 hom.)
• Consequence: SLC13A2 NM_003984.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270
• Publications: 10 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=0.009649694).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000834 (127/152344) while in subpopulation EAS AF = 0.023 (119/5180). AF 95% confidence interval is 0.0196. There are 2 homozygotes in GnomAd4. There are 66 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.130C>T	p.Leu44Phe	missense	Exon 2 of 12	NP_003975.1
	SLC13A2	NM_001145975.2		c.130C>T	p.Leu44Phe	missense	Exon 2 of 12	NP_001139447.1
	SLC13A2	NM_001346683.2		c.-3C>T		5_prime_UTR	Exon 3 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.130C>T	p.Leu44Phe	missense	Exon 2 of 12	ENSP00000316202.6
	RSKR	ENST00000481916.6	TSL:1	n.*1196-33132G>A		intron	N/A	ENSP00000436369.2
	SLC13A2	ENST00000444914.7	TSL:2	c.130C>T	p.Leu44Phe	missense	Exon 2 of 12	ENSP00000392411.3

Frequencies

GnomAD3 genomes AF: 0.000841 AC: 128 AN: 152226 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00164 AC: 411 AN: 251302 AF XY: 0.00151

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0210

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.00101 AC: 1470 AN: 1461686 Hom.: 28 Cov.: 30 AF XY: 0.000981 AC XY: 713 AN XY: 727160

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.0336 AC: 1334 AN: 39700

South Asian (SAS) AF: 0.000487 AC: 42 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53270

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5766

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1111974

Other (OTH) AF: 0.000662 AC: 40 AN: 60386

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152344 Hom.: 2 Cov.: 33 AF XY: 0.000886 AC XY: 66 AN XY: 74494

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0230 AC: 119 AN: 5180

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

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

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68040

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00105 Hom.: 8

Bravo AF: 0.000706

ExAC AF: 0.00195 AC: 237

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.69	D
LIST_S2	Uncertain	0.92	D
MetaRNN	Benign	0.0096	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.27
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.98	D
Vest4		0.40
MVP		0.51
MPC		0.96
ClinPred		0.089	T
GERP RS		2.4
Varity_R		0.24
gMVP		0.69
Mutation Taster		=290/10	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: rs45443898; hg19: chr17-26816259; COSMIC: COSV58994651;