16-31483188-G-C

Position:

chr16-31483188-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_003041.4(SLC5A2):c.52G>C(p.Ala18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000127 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SLC5A2
NM_003041.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

SLC5A2 (HGNC:11037): (solute carrier family 5 member 2) This gene encodes a member of the sodium glucose cotransporter family which are sodium-dependent glucose transport proteins. The encoded protein is the major cotransporter involved in glucose reabsorption in the kidney. Mutations in this gene are associated with renal glucosuria. Two transcript variants, one protein-coding and one not, have been found for this gene. [provided by RefSeq, Feb 2015]

SLC5A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.024759084).

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00013 (190/1461768) while in subpopulation MID AF= 0.00312 (18/5768). AF 95% confidence interval is 0.00202. There are 0 homozygotes in gnomad4_exome. There are 118 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC5A2	NM_003041.4 linkuse as main transcript	c.52G>C	p.Ala18Pro	missense_variant	1/14	ENST00000330498.4
SLC5A2	XM_006721072.5 linkuse as main transcript	c.52G>C	p.Ala18Pro	missense_variant	1/13
SLC5A2	XM_024450402.2 linkuse as main transcript	c.52G>C	p.Ala18Pro	missense_variant	1/11
SLC5A2	NR_130783.2 linkuse as main transcript	n.66G>C		non_coding_transcript_exon_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A2	ENST00000330498.4 linkuse as main transcript	c.52G>C	p.Ala18Pro	missense_variant	1/14	1	NM_003041.4	P1	P31639-1
SLC5A2	ENST00000419665.6 linkuse as main transcript	c.52G>C	p.Ala18Pro	missense_variant, NMD_transcript_variant	1/12	1			P31639-2
SLC5A2	ENST00000569576.5 linkuse as main transcript	c.-4+120G>C		intron_variant		4
SLC5A2	ENST00000562006.1 linkuse as main transcript	n.51G>C		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251324

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000130

AC:

190

AN:

1461768

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

118

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000585

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.52G>C (p.A18P) alteration is located in exon 1 (coding exon 1) of the SLC5A2 gene. This alteration results from a G to C substitution at nucleotide position 52, causing the alanine (A) at amino acid position 18 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.12

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.99

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.56

REVEL

Benign

0.17

Sift

Benign

0.27

Sift4G

Benign

0.21

Polyphen

0.16

Vest4

0.21

MVP

0.88

MPC

0.38

ClinPred

0.031

GERP RS

1.9

Varity_R

0.10

gMVP

0.78

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over