rs397515487
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP2PP5
The NM_005334.3(HCFC1):c.217G>A(p.Ala73Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A73V) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 22)
Consequence
HCFC1
NM_005334.3 missense
NM_005334.3 missense
Scores
5
5
7
Clinical Significance
Conservation
PhyloP100: 7.70
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 Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chrX-153964702-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 66985.We mark this variant Likely_pathogenic, oryginal submissions are: {not_provided=1, Uncertain_significance=1, Pathogenic=3}.
PP2
?
Missense variant where missense usually causes diseases, HCFC1
PP5
?
Variant X-153964703-C-T is Pathogenic according to our data. Variant chrX-153964703-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 66986.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCFC1 | NM_005334.3 | c.217G>A | p.Ala73Thr | missense_variant | 2/26 | ENST00000310441.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCFC1 | ENST00000310441.12 | c.217G>A | p.Ala73Thr | missense_variant | 2/26 | 1 | NM_005334.3 | P2 | |
HCFC1 | ENST00000369984.4 | c.217G>A | p.Ala73Thr | missense_variant | 2/26 | 5 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Methylmalonic acidemia with homocystinuria, type cblX Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 05, 2013 | - - |
Disorders of Intracellular Cobalamin Metabolism Other:1
not provided, no classification provided | literature only | GeneReviews | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T;T
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Gain of glycosylation at A73 (P = 0.02);Gain of glycosylation at A73 (P = 0.02);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at