chr10-87094394-C-T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_005271.5(GLUD1):c.376G>A(p.Asp126Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00153 in 1,613,326 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_005271.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLUD1 | NM_005271.5 | c.376G>A | p.Asp126Asn | missense_variant | Exon 1 of 13 | ENST00000277865.5 | NP_005262.1 | |
GLUD1 | NM_001318904.2 | c.-353G>A | 5_prime_UTR_variant | Exon 1 of 14 | NP_001305833.1 | |||
GLUD1 | NM_001318905.2 | c.-479G>A | 5_prime_UTR_variant | Exon 1 of 16 | NP_001305834.1 | |||
GLUD1 | NM_001318906.2 | c.-186G>A | 5_prime_UTR_variant | Exon 1 of 14 | NP_001305835.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00764 AC: 1162AN: 152134Hom.: 13 Cov.: 31
GnomAD3 exomes AF: 0.00209 AC: 522AN: 249766Hom.: 1 AF XY: 0.00159 AC XY: 216AN XY: 135476
GnomAD4 exome AF: 0.000892 AC: 1304AN: 1461078Hom.: 14 Cov.: 32 AF XY: 0.000791 AC XY: 575AN XY: 726854
GnomAD4 genome AF: 0.00765 AC: 1165AN: 152248Hom.: 13 Cov.: 31 AF XY: 0.00739 AC XY: 550AN XY: 74432
ClinVar
Submissions by phenotype
Hyperinsulinism-hyperammonemia syndrome Benign:2
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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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not provided Benign:2
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not specified Benign:1
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Monogenic diabetes Benign:1
ACMG criteria: BP5 (seen in patient with GCK pathogenic variant), BS2 (found in 74 controls in T2DM database and 58 cases) and BA1 (2.8% MAF in gnomAD AA and 9 Today study individuals has the same variant ): benign; NOTE: GLUD1 variants for hyperinsulinemia are found in exons 6, 7, 10, 11 and 12, this variant is in exon 1." (REVEL 0.318 + PP3/4 predictors + BP4/6 predictor: conflicting evidence, not using) -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at