Variant 16-31483138-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PVS1_Supporting

The NM_003041.4(SLC5A2):c.2T>C(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SLC5A2
NM_003041.4 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.635

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 Uncertain_significance. Variant got 1 ACMG points.

PVS1

Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 13 codons. Genomic position: 31483173. Lost 0.018 part of the original CDS.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A2	NM_003041.4 link	c.2T>C	p.Met1?	start_lost	Exon 1 of 14	ENST00000330498.4	NP_003032.1	P31639-1
SLC5A2	XM_006721072.5 link	c.2T>C	p.Met1?	start_lost	Exon 1 of 13		XP_006721135.3	Q8WY15
SLC5A2	XM_024450402.2 link	c.2T>C	p.Met1?	start_lost	Exon 1 of 11		XP_024306170.2
SLC5A2	NR_130783.2 link	n.16T>C		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC5A2	ENST00000330498.4 link	c.2T>C	p.Met1?	start_lost	Exon 1 of 14	1	NM_003041.4	ENSP00000327943.3	P31639-1
SLC5A2	ENST00000419665.6 link	n.2T>C		non_coding_transcript_exon_variant	Exon 1 of 12	1		ENSP00000410601.2	P31639-2
SLC5A2	ENST00000569576.5 link	c.-4+70T>C		intron_variant	Intron 1 of 4	4		ENSP00000455143.1	H3BP44
SLC5A2	ENST00000562006.1 link	n.1T>C		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251158

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461594

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151804

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74110

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Familial renal glucosuria

Uncertain:1

Mar 04, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.62

BayesDel_noAF

Uncertain

0.030

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.092

Eigen

Benign

0.11

Eigen_PC

Benign

0.094

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.83

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.31

PROVEAN

Benign

0.22

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0030

Polyphen

0.72

Vest4

0.79

MutPred

0.98

Gain of glycosylation at M1 (P = 0.0016);

MVP

0.94

ClinPred

0.99

GERP RS

3.9

Varity_R

0.76

gMVP

0.73

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