rs121434581
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001042.3(SLC2A4):c.1147G>A(p.Val383Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0056 in 1,614,176 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0040 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0058 ( 30 hom. )
Consequence
SLC2A4
NM_001042.3 missense
NM_001042.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 0.253
Genes affected
SLC2A4 (HGNC:11009): (solute carrier family 2 member 4) This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.009615719).
BS2
?
High Homozygotes in GnomAd at 3 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A4 | NM_001042.3 | c.1147G>A | p.Val383Ile | missense_variant | 10/11 | ENST00000317370.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A4 | ENST00000317370.13 | c.1147G>A | p.Val383Ile | missense_variant | 10/11 | 1 | NM_001042.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00404 AC: 615AN: 152182Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00417 AC: 1049AN: 251460Hom.: 4 AF XY: 0.00432 AC XY: 587AN XY: 135908
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GnomAD4 exome AF: 0.00577 AC: 8430AN: 1461876Hom.: 30 Cov.: 32 AF XY: 0.00565 AC XY: 4107AN XY: 727244
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GnomAD4 genome ? AF: 0.00404 AC: 615AN: 152300Hom.: 3 Cov.: 32 AF XY: 0.00371 AC XY: 276AN XY: 74478
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ESP6500AA
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ExAC
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ClinVar
Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Type 2 diabetes mellitus Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jan 01, 1995 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | SLC2A4: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
A;A;A
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Uncertain
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
B;.;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at