Genetic Variant NM_003984.4:c.1648A>C (chr17-28497138-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_003984.4(SLC13A2):c.1648A>C(p.Ile550Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC13A2
NM_003984.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.454

Publications

38 publications found

Variant links:

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]

SLC13A2 links:

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]

RSKR links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.055040866).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC13A2	NM_003984.4	MANE Select	c.1648A>C	p.Ile550Leu	missense	Exon 12 of 12	NP_003975.1
SLC13A2	NM_001145975.2		c.1795A>C	p.Ile599Leu	missense	Exon 12 of 12	NP_001139447.1
SLC13A2	NM_001346683.2		c.1516A>C	p.Ile506Leu	missense	Exon 13 of 13	NP_001333612.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC13A2	ENST00000314669.10	TSL:1 MANE Select	c.1648A>C	p.Ile550Leu	missense	Exon 12 of 12	ENSP00000316202.6
RSKR	ENST00000481916.6	TSL:1	n.*1196-41029T>G		intron	N/A	ENSP00000436369.2
SLC13A2	ENST00000855217.1		c.1798A>C	p.Ile600Leu	missense	Exon 12 of 12	ENSP00000525276.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111996

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

38918

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.039

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.53

M_CAP

Benign

0.0062

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.29

PhyloP100

0.45

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.37

REVEL

Benign

0.029

Sift

Benign

0.47

Sift4G

Benign

0.26

Polyphen

0.0080

Vest4

0.16

MutPred

0.45

Gain of catalytic residue at I550 (P = 0.0756)

MVP

0.14

MPC

0.27

ClinPred

0.15

GERP RS

3.2

Varity_R

0.096

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over