chr20-46725352-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_030777.4(SLC2A10):​c.316G>T​(p.Ala106Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00152 in 1,614,082 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 20 hom., cov: 33)
Exomes 𝑓: 0.00084 ( 19 hom. )

Consequence

SLC2A10
NM_030777.4 missense

Scores

18

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.380
Variant links:
Genes affected
SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004226029).
BP6
Variant 20-46725352-G-T is Benign according to our data. Variant chr20-46725352-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 139170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46725352-G-T is described in Lovd as [Benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00805 (1226/152334) while in subpopulation AFR AF= 0.0279 (1162/41584). AF 95% confidence interval is 0.0266. There are 20 homozygotes in gnomad4. There are 570 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC2A10NM_030777.4 linkc.316G>T p.Ala106Ser missense_variant Exon 2 of 5 ENST00000359271.4 NP_110404.1 O95528

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC2A10ENST00000359271.4 linkc.316G>T p.Ala106Ser missense_variant Exon 2 of 5 1 NM_030777.4 ENSP00000352216.2 O95528
SLC2A10ENST00000611837.1 linkn.468G>T non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
AF:
0.00803
AC:
1223
AN:
152216
Hom.:
20
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0280
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00301
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:
0.000147
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00226
AC:
566
AN:
250830
Hom.:
5
AF XY:
0.00173
AC XY:
235
AN XY:
135614
show subpopulations
Gnomad AFR exome
AF:
0.0308
Gnomad AMR exome
AF:
0.00145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000843
AC:
1232
AN:
1461748
Hom.:
19
Cov.:
33
AF XY:
0.000710
AC XY:
516
AN XY:
727178
show subpopulations
Gnomad4 AFR exome
AF:
0.0301
Gnomad4 AMR exome
AF:
0.00186
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000378
Gnomad4 OTH exome
AF:
0.00157
GnomAD4 genome
AF:
0.00805
AC:
1226
AN:
152334
Hom.:
20
Cov.:
33
AF XY:
0.00765
AC XY:
570
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.0279
Gnomad4 AMR
AF:
0.00300
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00143
Hom.:
46
Bravo
AF:
0.00949
ESP6500AA
AF:
0.0277
AC:
122
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00275
AC:
334
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Arterial tortuosity syndrome Benign:5
Nov 18, 2024
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 28, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jul 12, 2017
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 29, 2016
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not specified Benign:2
Feb 01, 2013
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Nov 07, 2021
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection Benign:2
Mar 21, 2017
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 02, 2015
Ambry Genetics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.068
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
0.10
DANN
Benign
0.85
DEOGEN2
Benign
0.18
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.048
T
MetaRNN
Benign
0.0042
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
1.0
L
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.99
N
REVEL
Benign
0.17
Sift
Benign
0.29
T
Sift4G
Benign
0.48
T
Polyphen
0.0020
B
Vest4
0.023
MVP
0.28
MPC
0.060
ClinPred
0.0012
T
GERP RS
-5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.055
gMVP
0.12

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: rs6094438; hg19: chr20-45353991; COSMIC: COSV63715126; API