rs372516617
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005334.3(HCFC1):āc.717C>Gā(p.Thr239=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000806 in 1,200,762 control chromosomes in the GnomAD database, including 1 homozygotes. There are 293 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00031 ( 0 hom., 9 hem., cov: 23)
Exomes š: 0.00086 ( 1 hom. 284 hem. )
Consequence
HCFC1
NM_005334.3 synonymous
NM_005334.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.55
Genes affected
HCFC1 (HGNC:4839): (host cell factor C1) This gene is a member of the host cell factor family and encodes a protein with five Kelch repeats, a fibronectin-like motif, and six HCF repeats, each of which contains a highly specific cleavage signal. This nuclear coactivator is proteolytically cleaved at one of the six possible sites, resulting in the creation of an N-terminal chain and the corresponding C-terminal chain. The final form of this protein consists of noncovalently bound N- and C-terminal chains. The protein is involved in control of the cell cycle and transcriptional regulation during herpes simplex virus infection. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant X-153962302-G-C is Benign according to our data. Variant chrX-153962302-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 435405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-2.55 with no splicing effect.
BS2
?
High Hemizygotes in GnomAd4 at 9 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCFC1 | NM_005334.3 | c.717C>G | p.Thr239= | synonymous_variant | 5/26 | ENST00000310441.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCFC1 | ENST00000310441.12 | c.717C>G | p.Thr239= | synonymous_variant | 5/26 | 1 | NM_005334.3 | P2 | |
HCFC1 | ENST00000369984.4 | c.717C>G | p.Thr239= | synonymous_variant | 5/26 | 5 | A2 | ||
HCFC1 | ENST00000461098.1 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000312 AC: 35AN: 112167Hom.: 0 Cov.: 23 AF XY: 0.000262 AC XY: 9AN XY: 34325
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GnomAD3 exomes AF: 0.000270 AC: 48AN: 177532Hom.: 0 AF XY: 0.000250 AC XY: 16AN XY: 64026
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GnomAD4 exome AF: 0.000857 AC: 933AN: 1088595Hom.: 1 Cov.: 28 AF XY: 0.000802 AC XY: 284AN XY: 354257
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GnomAD4 genome ? AF: 0.000312 AC: 35AN: 112167Hom.: 0 Cov.: 23 AF XY: 0.000262 AC XY: 9AN XY: 34325
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 07, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 25, 2016 | - - |
HCFC1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 06, 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). - |
Methylmalonic acidemia with homocystinuria, type cblX Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at