chr22-32043316-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 1P and 13B. PP2BP4_StrongBP6BS1BS2

The NM_000343.4(SLC5A1):​c.35C>T​(p.Ala12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000658 in 1,614,188 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00063 ( 7 hom. )

Consequence

SLC5A1
NM_000343.4 missense

Scores

2
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 1.11
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 Benign. Variant got -12 ACMG points.

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=0.004654914).
BP6
Variant 22-32043316-C-T is Benign according to our data. Variant chr22-32043316-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 502121.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=2}.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000919 (140/152354) while in subpopulation AMR AF= 0.00118 (18/15308). AF 95% confidence interval is 0.00076. There are 0 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC5A1NM_000343.4 linkuse as main transcriptc.35C>T p.Ala12Val missense_variant 1/15 ENST00000266088.9 NP_000334.1
SLC5A1XM_011530331.2 linkuse as main transcriptc.35C>T p.Ala12Val 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.35C>T p.Ala12Val missense_variant 1/151 NM_000343.4 ENSP00000266088 P1P13866-1

Frequencies

GnomAD3 genomes
AF:
0.000920
AC:
140
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.0199
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000828
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000573
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00113
AC:
284
AN:
250746
Hom.:
5
AF XY:
0.00128
AC XY:
174
AN XY:
135618
show subpopulations
Gnomad AFR exome
AF:
0.0000618
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.0161
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00101
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000608
Gnomad OTH exome
AF:
0.00196
GnomAD4 exome
AF:
0.000631
AC:
922
AN:
1461834
Hom.:
7
Cov.:
32
AF XY:
0.000674
AC XY:
490
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.0145
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000997
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000307
Gnomad4 OTH exome
AF:
0.00142
GnomAD4 genome
AF:
0.000919
AC:
140
AN:
152354
Hom.:
0
Cov.:
32
AF XY:
0.000940
AC XY:
70
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.0199
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000829
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.000573
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00123
Hom.:
2
Bravo
AF:
0.000854
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00105
AC:
9
ExAC
AF:
0.000955
AC:
116
EpiCase
AF:
0.00125
EpiControl
AF:
0.000948

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Congenital glucose-galactose malabsorption Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 31, 2024- -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2023SLC5A1: PM2:Supporting, PP4, BP4 -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)May 30, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.085
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.10
CADD
Benign
10
DANN
Uncertain
0.99
DEOGEN2
Benign
0.090
T
Eigen
Benign
-0.76
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.083
N
LIST_S2
Benign
0.33
T
M_CAP
Benign
0.085
D
MetaRNN
Benign
0.0047
T
MetaSVM
Benign
-0.70
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.5
N
REVEL
Uncertain
0.51
Sift
Benign
0.061
T
Sift4G
Benign
0.41
T
Polyphen
0.0010
B
Vest4
0.061
MVP
0.75
MPC
0.46
ClinPred
0.017
T
GERP RS
3.7
Varity_R
0.067
gMVP
0.27

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: rs150288967; hg19: chr22-32439303; API