rs76362149
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_000340.2(SLC2A2):c.1087G>T(p.Ala363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,610,670 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 2 hom. )
Consequence
SLC2A2
NM_000340.2 missense
NM_000340.2 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 3.09
Genes affected
SLC2A2 (HGNC:11006): (solute carrier family 2 member 2) This gene encodes an integral plasma membrane glycoprotein of the liver, islet beta cells, intestine, and kidney epithelium. The encoded protein mediates facilitated bidirectional glucose transport. Because of its low affinity for glucose, it has been suggested as a glucose sensor. Mutations in this gene are associated with susceptibility to diseases, including Fanconi-Bickel syndrome and noninsulin-dependent diabetes mellitus (NIDDM). Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.031058013).
BP6
?
Variant 3-170999148-C-A is Benign according to our data. Variant chr3-170999148-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 199012.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=2}. Variant chr3-170999148-C-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00108 (165/152166) while in subpopulation NFE AF= 0.00159 (108/67990). AF 95% confidence interval is 0.00135. There are 0 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A2 | NM_000340.2 | c.1087G>T | p.Ala363Ser | missense_variant | 9/11 | ENST00000314251.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A2 | ENST00000314251.8 | c.1087G>T | p.Ala363Ser | missense_variant | 9/11 | 1 | NM_000340.2 | P1 | |
SLC2A2 | ENST00000497642.5 | c.*554G>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/10 | 1 | ||||
ENST00000655926.1 | n.291+4123C>A | intron_variant, non_coding_transcript_variant | |||||||
SLC2A2 | ENST00000469787.1 | c.*554G>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/10 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00109 AC: 165AN: 152048Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00153 AC: 384AN: 250756Hom.: 0 AF XY: 0.00147 AC XY: 199AN XY: 135506
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GnomAD4 exome AF: 0.00160 AC: 2327AN: 1458504Hom.: 2 Cov.: 29 AF XY: 0.00156 AC XY: 1131AN XY: 725744
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Fanconi-Bickel syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 23, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 09, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Reported as a heterozygous SNP in an individual with myelomeningocele (Ruggiero et al., 2015); This variant is associated with the following publications: (PMID: 30950137, 25776730) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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