chr16-31484743-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3

The NM_003041.4(SLC5A2):​c.197C>T​(p.Pro66Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000112 in 1,610,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC5A2
NM_003041.4 missense, splice_region

Scores

5
9
5
Splicing: ADA: 0.9983
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.80
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC5A2NM_003041.4 linkuse as main transcriptc.197C>T p.Pro66Leu missense_variant, splice_region_variant 2/14 ENST00000330498.4
SLC5A2XM_006721072.5 linkuse as main transcriptc.197C>T p.Pro66Leu missense_variant, splice_region_variant 2/13
SLC5A2XM_024450402.2 linkuse as main transcriptc.197C>T p.Pro66Leu missense_variant, splice_region_variant 2/11
SLC5A2NR_130783.2 linkuse as main transcriptn.211C>T splice_region_variant, non_coding_transcript_exon_variant 2/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC5A2ENST00000330498.4 linkuse as main transcriptc.197C>T p.Pro66Leu missense_variant, splice_region_variant 2/141 NM_003041.4 P1P31639-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152204
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000121
AC:
3
AN:
248562
Hom.:
0
AF XY:
0.00000743
AC XY:
1
AN XY:
134650
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
16
AN:
1458204
Hom.:
0
Cov.:
32
AF XY:
0.00000827
AC XY:
6
AN XY:
725614
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.0000126
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152204
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74358
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3
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
Uncertain significance, criteria provided, single submitterclinical testingMVZ Medizinische Genetik MainzNov 08, 2021PM2_SUP, PP3, PP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.31
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Benign
0.073
T;T
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Uncertain
0.18
D
MetaRNN
Pathogenic
0.85
D;D
MetaSVM
Uncertain
0.34
D
MutationAssessor
Benign
2.0
.;M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-8.6
D;D
REVEL
Pathogenic
0.73
Sift
Benign
0.20
T;T
Sift4G
Uncertain
0.036
D;T
Polyphen
1.0
.;D
Vest4
0.58
MutPred
0.67
.;Gain of MoRF binding (P = 0.0456);
MVP
0.95
MPC
0.57
ClinPred
0.98
D
GERP RS
5.1
Varity_R
0.60
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.82
SpliceAI score (max)
0.090
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.

Other links and lift over

dbSNP: rs746746841; hg19: chr16-31496064; COSMIC: COSV57891632; COSMIC: COSV57891632; API