rs782332238

chrX-153955129-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005334.3(HCFC1):c.3270C>T(p.Thr1090=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,206,798 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.000012 (0 hom. 4 hem.)
• Consequence: HCFC1 NM_005334.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.72

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]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant X-153955129-G-A is Benign according to our data. Variant chrX-153955129-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153955129-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-4.72 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCFC1	NM_005334.3	c.3270C>T	p.Thr1090=	synonymous_variant	17/26	ENST00000310441.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCFC1	ENST00000310441.12	c.3270C>T	p.Thr1090=	synonymous_variant	17/26	1	NM_005334.3	P2
HCFC1	ENST00000369984.4	c.3270C>T	p.Thr1090=	synonymous_variant	17/26	5		A2

Frequencies

GnomAD3 genomes AF: 0.00000912 AC: 1 AN: 109637 Hom.: 0 Cov.: 24 AF XY: 0.0000308 AC XY: 1 AN XY: 32459

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000191

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000223 AC: 4 AN: 179558 Hom.: 0 AF XY: 0.0000302 AC XY: 2 AN XY: 66256

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000110

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: 0.0000125

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000118 AC: 13 AN: 1097161 Hom.: 0 Cov.: 34 AF XY: 0.0000110 AC XY: 4 AN XY: 362705

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000855

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: 0.0000107

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome AF: 0.00000912 AC: 1 AN: 109637 Hom.: 0 Cov.: 24 AF XY: 0.0000308 AC XY: 1 AN XY: 32459

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000191

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Feb 27, 2017

- -

Methylmalonic acidemia with homocystinuria, type cblX Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.53
Dann	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		3.0

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

Other links and lift over

dbSNP: rs782332238; hg19: chrX-153220580; COSMIC: COSV60073593; COSMIC: COSV60073593;