X-153949054-G-A

Position:

• chrX-153949054-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005334.3(HCFC1):​c.*293C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 233,627 control chromosomes in the GnomAD database, including 120 homozygotes. There are 964 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (98 hom., 861 hem., cov: 22)
  • Exomes 𝑓: 0.0041 (22 hom. 103 hem.)
• Consequence: HCFC1 NM_005334.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.676

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant X-153949054-G-A is Benign according to our data. Variant chrX-153949054-G-A is described in ClinVar as [Benign]. Clinvar id is 1265668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCFC1	NM_005334.3	c.*293C>T		3_prime_UTR_variant	26/26	ENST00000310441.12	NP_005325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCFC1	ENST00000310441.12	c.*293C>T		3_prime_UTR_variant	26/26	1	NM_005334.3	ENSP00000309555	P2
HCFC1	ENST00000369984.4	c.*293C>T		3_prime_UTR_variant	26/26	5		ENSP00000359001	A2
HCFC1	ENST00000444191.5	c.*293C>T		3_prime_UTR_variant	10/10	5		ENSP00000399589

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 3070 AN: 110503 Hom.: 96 Cov.: 22 AF XY: 0.0258 AC XY: 847 AN XY: 32791

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00851

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.00414 AC: 510 AN: 123076 Hom.: 22 Cov.: 0 AF XY: 0.00397 AC XY: 103 AN XY: 25950

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.00551

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000114

Gnomad4 OTH exome AF: 0.00679

GnomAD4 genome AF: 0.0280 AC: 3091 AN: 110551 Hom.: 98 Cov.: 22 AF XY: 0.0262 AC XY: 861 AN XY: 32849

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0247 Hom.: 74

Bravo AF: 0.0322

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.82
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.2

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: rs190463296; hg19: chrX-153214505;