rs190023981
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_005334.3(HCFC1):c.2590G>A(p.Ala864Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00157 in 1,210,086 control chromosomes in the GnomAD database, including 3 homozygotes. There are 627 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A864A) has been classified as Likely benign.
Frequency
Consequence
NM_005334.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCFC1 | NM_005334.3 | c.2590G>A | p.Ala864Thr | missense_variant | 15/26 | ENST00000310441.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCFC1 | ENST00000310441.12 | c.2590G>A | p.Ala864Thr | missense_variant | 15/26 | 1 | NM_005334.3 | P2 | |
HCFC1 | ENST00000369984.4 | c.2590G>A | p.Ala864Thr | missense_variant | 15/26 | 5 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000720 AC: 81AN: 112425Hom.: 0 Cov.: 24 AF XY: 0.000781 AC XY: 27AN XY: 34589
GnomAD3 exomes AF: 0.000722 AC: 131AN: 181435Hom.: 0 AF XY: 0.000651 AC XY: 44AN XY: 67541
GnomAD4 exome AF: 0.00166 AC: 1819AN: 1097608Hom.: 3 Cov.: 32 AF XY: 0.00165 AC XY: 600AN XY: 363206
GnomAD4 genome ? AF: 0.000720 AC: 81AN: 112478Hom.: 0 Cov.: 24 AF XY: 0.000779 AC XY: 27AN XY: 34652
ClinVar
Submissions by phenotype
not specified Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 13, 2015 | - - |
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 | Genetic Services Laboratory, University of Chicago | Jan 20, 2016 | - - |
Methylmalonic acidemia with homocystinuria, type cblX Benign:2
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 25, 2019 | This variant is associated with the following publications: (PMID: 25595573, 26893841) - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
HCFC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 14, 2021 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at