16-31484846-A-G

Variant summary

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

The NM_003041.4(SLC5A2):ā€‹c.226A>Gā€‹(p.Ile76Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,613,832 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I76N) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.000019 ( 0 hom. )

Consequence

SLC5A2
NM_003041.4 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20
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 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC5A2NM_003041.4 linkuse as main transcriptc.226A>G p.Ile76Val missense_variant 3/14 ENST00000330498.4
SLC5A2XM_006721072.5 linkuse as main transcriptc.226A>G p.Ile76Val missense_variant 3/13
SLC5A2XM_024450402.2 linkuse as main transcriptc.226A>G p.Ile76Val missense_variant 3/11
SLC5A2NR_130783.2 linkuse as main transcriptn.240A>G non_coding_transcript_exon_variant 3/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC5A2ENST00000330498.4 linkuse as main transcriptc.226A>G p.Ile76Val missense_variant 3/141 NM_003041.4 P1P31639-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251016
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135754
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000192
AC:
28
AN:
1461598
Hom.:
0
Cov.:
32
AF XY:
0.0000179
AC XY:
13
AN XY:
727110
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
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:
0.0000216
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152234
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000165
AC:
2
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 testingNew York Genome CenterApr 29, 2022The c.226A>G (p.Ile76Val) missense variant identified in the SLC5A2 gene has not been reported in affected individuals in theliterature. The variant has a 0.00001314allele frequency in the gnomAD(v3) database (2 out of 152,234 heterozygous alleles, no homozygotes) suggesting it is not a common benign variant in the populations represented in that database. The variant affects an evolutionarily conserved residue and in silico predictions are inconclusive of the variant's effect (CADD v1.6 = 23.3, REVEL = 0.570); however, there are no functional studies to support or refute these predictions. Based on the available evidence, the c.226A>G (p.Ile76Val) missense variant identified in the SLC5A2 gene is reported as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
0.011
T
BayesDel_noAF
Benign
-0.14
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.011
T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.51
T;T
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.56
D;D
MetaSVM
Uncertain
0.50
D
MutationAssessor
Benign
0.93
.;L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-0.74
N;N
REVEL
Uncertain
0.57
Sift
Benign
0.31
T;T
Sift4G
Benign
0.33
T;T
Polyphen
0.99
.;D
Vest4
0.33
MutPred
0.79
.;Gain of disorder (P = 0.1592);
MVP
0.88
MPC
0.65
ClinPred
0.51
D
GERP RS
5.1
Varity_R
0.20
gMVP
0.62

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.

Other links and lift over

dbSNP: rs750542045; hg19: chr16-31496167; API