X-153946200-A-G

Variant names:

• chrX-153946200-A-G
• rs762656
• ENST00000925197.1:c.*3147T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000925197.1(HCFC1):​c.*3147T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 111,723 control chromosomes in the GnomAD database, including 7,999 homozygotes. There are 12,960 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (7999 hom., 12960 hem., cov: 24)
• Consequence: HCFC1 ENST00000925197.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.444
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• methylmalonic acidemia with homocystinuria, type cblX

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• X-linked intellectual disability

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• non-syndromic X-linked intellectual disability

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000925197.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCFC1	ENST00000925197.1		c.*3147T>C		downstream_gene	N/A	ENSP00000595256.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 42622 AN: 111672 Hom.: 7990 Cov.: 24

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.0705

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.404

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.382 AC: 42680 AN: 111723 Hom.: 7999 Cov.: 24 AF XY: 0.382 AC XY: 12960 AN XY: 33963

African (AFR) AF: 0.685 AC: 21010 AN: 30656

American (AMR) AF: 0.498 AC: 5302 AN: 10650

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 680 AN: 2639

East Asian (EAS) AF: 0.760 AC: 2658 AN: 3498

South Asian (SAS) AF: 0.598 AC: 1606 AN: 2684

European-Finnish (FIN) AF: 0.174 AC: 1071 AN: 6139

Middle Eastern (MID) AF: 0.373 AC: 81 AN: 217

European-Non Finnish (NFE) AF: 0.181 AC: 9593 AN: 53034

Other (OTH) AF: 0.414 AC: 631 AN: 1525

Alfa AF: 0.299 Hom.: 2014

Bravo AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.67
DANN	Benign	0.54
PhyloP100		-0.44

Splicing

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

Other links and lift over

dbSNP: rs762656; hg19: chrX-153211652;