rs34085965
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_000520.6(HEXA):āc.1338T>Cā(p.Pro446=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000349 in 1,613,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. P446P) has been classified as Likely benign.
Frequency
Consequence
NM_000520.6 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HEXA | NM_000520.6 | c.1338T>C | p.Pro446= | synonymous_variant | 12/14 | ENST00000268097.10 | |
HEXA | NM_001318825.2 | c.1371T>C | p.Pro457= | synonymous_variant | 12/14 | ||
HEXA | NR_134869.3 | n.1123T>C | non_coding_transcript_exon_variant | 10/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HEXA | ENST00000268097.10 | c.1338T>C | p.Pro446= | synonymous_variant | 12/14 | 1 | NM_000520.6 | P1 | |
ENST00000570175.1 | n.1098A>G | non_coding_transcript_exon_variant | 2/3 | 1 |
Frequencies
GnomAD3 genomes AF: 0.000283 AC: 43AN: 152166Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000251 AC: 63AN: 250932Hom.: 0 AF XY: 0.000265 AC XY: 36AN XY: 135640
GnomAD4 exome AF: 0.000356 AC: 520AN: 1461348Hom.: 0 Cov.: 30 AF XY: 0.000359 AC XY: 261AN XY: 726990
GnomAD4 genome AF: 0.000282 AC: 43AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74476
ClinVar
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2023 | HEXA: BP4, BP7 - |
Tay-Sachs disease Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
HEXA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 25, 2022 | This alteration is classified as likely 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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at