chrX-153961975-A-G

Variant names:

• chrX-153961975-A-G
• rs17422
• NM_005334.3:c.797+247T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005334.3(HCFC1):​c.797+247T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 111,255 control chromosomes in the GnomAD database, including 8,004 homozygotes. There are 12,775 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.38 (8004 hom., 12775 hem., cov: 23)
• Consequence: HCFC1 NM_005334.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.933
• Publications: 11 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• X-linked intellectual disability

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

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-153961975-A-G is Benign according to our data. Variant chrX-153961975-A-G is described in ClinVar as Benign. ClinVar VariationId is 671518.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005334.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCFC1	NM_005334.3	MANE Select	c.797+247T>C		intron	N/A	NP_005325.2	P51610-1
	HCFC1	NM_001440843.1		c.797+247T>C		intron	N/A	NP_001427772.1
	HCFC1	NM_001410705.1		c.797+247T>C		intron	N/A	NP_001397634.1	A6NEM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCFC1	ENST00000310441.12	TSL:1 MANE Select	c.797+247T>C		intron	N/A	ENSP00000309555.7	P51610-1
	HCFC1	ENST00000925202.1		c.797+247T>C		intron	N/A	ENSP00000595261.1
	HCFC1	ENST00000369984.4	TSL:5	c.797+247T>C		intron	N/A	ENSP00000359001.4	A6NEM2

Frequencies

GnomAD3 genomes AF: 0.382 AC: 42447 AN: 111198 Hom.: 7994 Cov.: 23

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.382 AC: 42508 AN: 111255 Hom.: 8004 Cov.: 23 AF XY: 0.382 AC XY: 12775 AN XY: 33485

African (AFR) AF: 0.687 AC: 20936 AN: 30456

American (AMR) AF: 0.498 AC: 5264 AN: 10573

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 680 AN: 2634

East Asian (EAS) AF: 0.759 AC: 2651 AN: 3493

South Asian (SAS) AF: 0.598 AC: 1587 AN: 2655

European-Finnish (FIN) AF: 0.178 AC: 1083 AN: 6075

Middle Eastern (MID) AF: 0.361 AC: 78 AN: 216

European-Non Finnish (NFE) AF: 0.180 AC: 9552 AN: 52943

Other (OTH) AF: 0.412 AC: 628 AN: 1524

Alfa AF: 0.260 Hom.: 6767

Bravo AF: 0.424

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.61
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17422; hg19: chrX-153227426;