rs782370052

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

Scores

4
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.24
Variant links:
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]

Genome browser will be placed here

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
HCFC1NM_005334.3 linkuse as main transcriptc.4001C>T p.Thr1334Ile missense_variant 17/26 ENST00000310441.12 NP_005325.2 P51610-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HCFC1ENST00000310441.12 linkuse as main transcriptc.4001C>T p.Thr1334Ile missense_variant 17/261 NM_005334.3 ENSP00000309555.7 P51610-1
HCFC1ENST00000369984.4 linkuse as main transcriptc.4001C>T p.Thr1334Ile missense_variant 17/265 ENSP00000359001.4 A6NEM2

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD3 exomes
AF:
0.0000111
AC:
2
AN:
179546
Hom.:
0
AF XY:
0.0000151
AC XY:
1
AN XY:
66108
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000250
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000155
AC:
17
AN:
1097345
Hom.:
0
Cov.:
34
AF XY:
0.0000165
AC XY:
6
AN XY:
362885
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000202
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
25
ExAC
AF:
0.00000826
AC:
1

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 submitterclinical testingAmbry GeneticsFeb 12, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.60
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.46
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T;T
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Pathogenic
0.40
D
MetaRNN
Uncertain
0.48
T;T
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.0
M;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-3.1
D;D
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.052
T;D
Polyphen
0.98
D;.
Vest4
0.47
MutPred
0.30
Loss of glycosylation at T1334 (P = 0.0011);Loss of glycosylation at T1334 (P = 0.0011);
MVP
0.60
MPC
1.5
ClinPred
0.91
D
GERP RS
5.6
Varity_R
0.71
gMVP
0.70

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782370052; hg19: chrX-153219849; API