rs782370052
Positions:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_005334.3(HCFC1):c.4001C>T(p.Thr1334Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,097,345 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 25)
Exomes 𝑓: 0.000015 ( 0 hom. 6 hem. )
Consequence
HCFC1
NM_005334.3 missense
NM_005334.3 missense
Scores
4
7
6
Clinical Significance
Conservation
PhyloP100: 9.24
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_benign. Variant got -3 ACMG points.
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HCFC1. . Gene score misZ 5.6341 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked intellectual disability, non-syndromic X-linked intellectual disability, methylmalonic acidemia with homocystinuria, type cblX.
BS2
High Hemizygotes in GnomAdExome4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HCFC1 | NM_005334.3 | c.4001C>T | p.Thr1334Ile | missense_variant | 17/26 | ENST00000310441.12 | NP_005325.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HCFC1 | ENST00000310441.12 | c.4001C>T | p.Thr1334Ile | missense_variant | 17/26 | 1 | NM_005334.3 | ENSP00000309555.7 | ||
HCFC1 | ENST00000369984.4 | c.4001C>T | p.Thr1334Ile | missense_variant | 17/26 | 5 | ENSP00000359001.4 |
Frequencies
GnomAD3 genomes Cov.: 25
GnomAD3 genomes
Cov.:
25
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 179546Hom.: 0 AF XY: 0.0000151 AC XY: 1AN XY: 66108
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GnomAD4 exome AF: 0.0000155 AC: 17AN: 1097345Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 6AN XY: 362885
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GnomAD4 genome Cov.: 25
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25
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Benign
Sift
Pathogenic
D;D
Sift4G
Uncertain
T;D
Polyphen
D;.
Vest4
MutPred
Loss of glycosylation at T1334 (P = 0.0011);Loss of glycosylation at T1334 (P = 0.0011);
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