chrX-153949560-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_005334.3(HCFC1):c.6061C>T(p.Pro2021Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,208,893 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )
Consequence
HCFC1
NM_005334.3 missense
NM_005334.3 missense
Scores
8
9
Clinical Significance
Conservation
PhyloP100: 8.26
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, HCFC1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.30340126).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCFC1 | NM_005334.3 | c.6061C>T | p.Pro2021Ser | missense_variant | 25/26 | ENST00000310441.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCFC1 | ENST00000310441.12 | c.6061C>T | p.Pro2021Ser | missense_variant | 25/26 | 1 | NM_005334.3 | P2 | |
HCFC1 | ENST00000369984.4 | c.6196C>T | p.Pro2066Ser | missense_variant | 25/26 | 5 | A2 | ||
HCFC1 | ENST00000444191.5 | c.1789C>T | p.Pro597Ser | missense_variant | 9/10 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000891 AC: 1AN: 112226Hom.: 0 Cov.: 24 AF XY: 0.0000291 AC XY: 1AN XY: 34370
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GnomAD4 exome AF: 9.12e-7 AC: 1AN: 1096667Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 362081
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GnomAD4 genome ? AF: 0.00000891 AC: 1AN: 112226Hom.: 0 Cov.: 24 AF XY: 0.0000291 AC XY: 1AN XY: 34370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 15, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Gain of phosphorylation at P2021 (P = 0.0012);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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