X-153954214-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005334.3(HCFC1):c.4185G>A(p.Ala1395Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,205,918 control chromosomes in the GnomAD database, including 27,269 homozygotes. There are 91,326 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 2573 hom., 7135 hem., cov: 24)

Exomes 𝑓: 0.22 ( 24696 hom. 84191 hem. )

Consequence

HCFC1
NM_005334.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-153954214-C-T is Benign according to our data. Variant chrX-153954214-C-T is described in ClinVar as [Benign]. Clinvar id is 95280.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153954214-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.78 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCFC1	NM_005334.3 link	c.4185G>A	p.Ala1395Ala	synonymous_variant	Exon 17 of 26	ENST00000310441.12	NP_005325.2	P51610-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HCFC1	ENST00000310441.12 link	c.4185G>A	p.Ala1395Ala	synonymous_variant	Exon 17 of 26	1	NM_005334.3	ENSP00000309555.7	P51610-1
HCFC1	ENST00000369984.4 link	c.4185G>A	p.Ala1395Ala	synonymous_variant	Exon 17 of 26	5		ENSP00000359001.4	A6NEM2
HCFC1	ENST00000444191.5 link	c.-94G>A		upstream_gene_variant		5		ENSP00000399589.1	H7C1C4

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

23129

AN:

109666

Hom.:

2567

Cov.:

AF XY:

0.221

AC XY:

7130

AN XY:

32210

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.0666

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.174

Gnomad OTH

AF:

0.254

GnomAD3 exomes

AF:

0.328

AC:

58117

AN:

177373

Hom.:

9057

AF XY:

0.325

AC XY:

21135

AN XY:

64953

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.592

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.762

Gnomad SAS exome

AF:

0.573

Gnomad FIN exome

AF:

0.181

Gnomad NFE exome

AF:

0.172

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.220

AC:

241644

AN:

1096205

Hom.:

24696

Cov.:

AF XY:

0.232

AC XY:

84191

AN XY:

362177

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.572

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.748

Gnomad4 SAS exome

AF:

0.568

Gnomad4 FIN exome

AF:

0.176

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.211

AC:

23136

AN:

109713

Hom.:

2573

Cov.:

AF XY:

0.221

AC XY:

7135

AN XY:

32267

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.424

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.760

Gnomad4 SAS

AF:

0.590

Gnomad4 FIN

AF:

0.172

Gnomad4 NFE

AF:

0.174

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.199

Hom.:

2393

Bravo

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 16, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Methylmalonic acidemia with homocystinuria, type cblX

Benign:2

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.092

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over