chr15-72346551-T-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000520.6(HEXA):āc.1306A>Gā(p.Ile436Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.978 in 1,613,876 control chromosomes in the GnomAD database, including 778,194 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 Benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I436L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000520.6 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.1306A>G | p.Ile436Val | missense_variant | 11/14 | ENST00000268097.10 | |
HEXA | NM_001318825.2 | c.1339A>G | p.Ile447Val | missense_variant | 11/14 | ||
HEXA | NR_134869.3 | n.1116-226A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.1306A>G | p.Ile436Val | missense_variant | 11/14 | 1 | NM_000520.6 | P1 | |
ENST00000570175.1 | n.1331T>C | non_coding_transcript_exon_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.889 AC: 135134AN: 152046Hom.: 62290 Cov.: 31
GnomAD3 exomes AF: 0.970 AC: 243905AN: 251366Hom.: 119523 AF XY: 0.979 AC XY: 132973AN XY: 135884
GnomAD4 exome AF: 0.988 AC: 1443888AN: 1461712Hom.: 715886 Cov.: 55 AF XY: 0.989 AC XY: 719363AN XY: 727168
GnomAD4 genome AF: 0.889 AC: 135203AN: 152164Hom.: 62308 Cov.: 31 AF XY: 0.892 AC XY: 66352AN XY: 74394
ClinVar
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 22, 2017 | - - |
Tay-Sachs disease Benign:5
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 29, 2017 | - - |
not provided Benign:4
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 23, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Mar 05, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at