Variant X-153949575-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2PP2PP5_ModerateBP4

The NM_005334.3(HCFC1):c.6046C>T(p.Arg2016Trp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 23)

Consequence

HCFC1
NM_005334.3 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.40

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]

HCFC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.

PP5

Variant X-153949575-G-A is Pathogenic according to our data. Variant chrX-153949575-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1299214.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.30411488). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCFC1	NM_005334.3 linkuse as main transcript	c.6046C>T	p.Arg2016Trp	missense_variant	25/26	ENST00000310441.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCFC1	ENST00000310441.12 linkuse as main transcript	c.6046C>T	p.Arg2016Trp	missense_variant	25/26	1	NM_005334.3	P2	P51610-1
HCFC1	ENST00000369984.4 linkuse as main transcript	c.6181C>T	p.Arg2061Trp	missense_variant	25/26	5		A2
HCFC1	ENST00000444191.5 linkuse as main transcript	c.1774C>T	p.Arg592Trp	missense_variant	9/10	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

T;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.0

M;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-4.2

D;D

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;.

Vest4

0.39

MutPred

0.15

Gain of ubiquitination at K2015 (P = 0.0268);.;

MVP

0.72

MPC

3.1

ClinPred

1.0

GERP RS

4.5

Varity_R

0.88

gMVP

0.91

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over