rs199511876
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_005334.3(HCFC1):c.5418G>A(p.Met1806Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00104 in 1,209,757 control chromosomes in the GnomAD database, including 2 homozygotes. There are 402 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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.5418G>A | p.Met1806Ile | missense_variant | 22/26 | ENST00000310441.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCFC1 | ENST00000310441.12 | c.5418G>A | p.Met1806Ile | missense_variant | 22/26 | 1 | NM_005334.3 | P2 | |
HCFC1 | ENST00000369984.4 | c.5553G>A | p.Met1851Ile | missense_variant | 22/26 | 5 | A2 | ||
HCFC1 | ENST00000444191.5 | c.1146G>A | p.Met382Ile | missense_variant | 6/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000947 AC: 106AN: 111960Hom.: 0 Cov.: 24 AF XY: 0.000674 AC XY: 23AN XY: 34140
GnomAD3 exomes AF: 0.000743 AC: 135AN: 181717Hom.: 1 AF XY: 0.000814 AC XY: 55AN XY: 67573
GnomAD4 exome AF: 0.00105 AC: 1156AN: 1097743Hom.: 2 Cov.: 32 AF XY: 0.00104 AC XY: 379AN XY: 363191
GnomAD4 genome ? AF: 0.000946 AC: 106AN: 112014Hom.: 0 Cov.: 24 AF XY: 0.000672 AC XY: 23AN XY: 34204
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 22, 2016 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 18, 2018 | - - |
Methylmalonic acidemia with homocystinuria, type cblX Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
HCFC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 28, 2022 | 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