22-32043322-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_000343.4(SLC5A1):​c.41C>T​(p.Thr14Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC5A1
NM_000343.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0850
Variant links:
Genes affected
SLC5A1 (HGNC:11036): (solute carrier family 5 member 1) This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC5A1. . Gene score misZ 1.833 (greater than the threshold 3.09). Trascript score misZ 3.1348 (greater than threshold 3.09). GenCC has associacion of gene with glucose-galactose malabsorption.
BP4
Computational evidence support a benign effect (MetaRNN=0.12005159).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC5A1NM_000343.4 linkuse as main transcriptc.41C>T p.Thr14Ile missense_variant 1/15 ENST00000266088.9 NP_000334.1
SLC5A1XM_011530331.2 linkuse as main transcriptc.41C>T p.Thr14Ile missense_variant 1/12 XP_011528633.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC5A1ENST00000266088.9 linkuse as main transcriptc.41C>T p.Thr14Ile missense_variant 1/151 NM_000343.4 ENSP00000266088 P1P13866-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461844
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Congenital glucose-galactose malabsorption Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 23, 2021This sequence change replaces threonine with isoleucine at codon 14 of the SLC5A1 protein (p.Thr14Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with SLC5A1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
5.0
DANN
Benign
0.89
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.88
FATHMM_MKL
Benign
0.060
N
LIST_S2
Benign
0.39
T
M_CAP
Benign
0.044
D
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.17
Sift
Benign
0.19
T
Sift4G
Benign
0.23
T
Polyphen
0.012
B
Vest4
0.096
MutPred
0.36
Loss of disorder (P = 0.0149);
MVP
0.76
MPC
0.53
ClinPred
0.096
T
GERP RS
1.5
Varity_R
0.063
gMVP
0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-32439309; API