X-153949297-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_005334.3(HCFC1):c.*50G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,116,965 control chromosomes in the GnomAD database, including 18 homozygotes. There are 1,696 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 0.0042 (0 hom., 115 hem., cov: 23)
  • Exomes 𝑓: 0.0051 (18 hom. 1581 hem.)
• Consequence: HCFC1 NM_005334.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.49

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant X-153949297-C-T is Benign according to our data. Variant chrX-153949297-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326428.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 115 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HCFC1	NM_005334.3	c.*50G>A		3_prime_UTR_variant	26/26	ENST00000310441.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCFC1	ENST00000310441.12	c.*50G>A		3_prime_UTR_variant	26/26	1	NM_005334.3	P2
HCFC1	ENST00000369984.4	c.*50G>A		3_prime_UTR_variant	26/26	5		A2
HCFC1	ENST00000444191.5	c.*50G>A		3_prime_UTR_variant	10/10	5

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 468 AN: 110258 Hom.: 0 Cov.: 23 AF XY: 0.00353 AC XY: 115 AN XY: 32536

Gnomad AFR AF: 0.000662

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00344

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00271

Gnomad FIN AF: 0.00374

Gnomad MID AF: 0.00847

Gnomad NFE AF: 0.00595

Gnomad OTH AF: 0.00399

GnomAD3 exomes AF: 0.00513 AC: 851 AN: 165970 Hom.: 5 AF XY: 0.00509 AC XY: 284 AN XY: 55788

Gnomad AFR exome AF: 0.000665

Gnomad AMR exome AF: 0.00211

Gnomad ASJ exome AF: 0.0277

Gnomad EAS exome AF: 0.0000782

Gnomad SAS exome AF: 0.00215

Gnomad FIN exome AF: 0.00685

Gnomad NFE exome AF: 0.00590

Gnomad OTH exome AF: 0.00865

GnomAD4 exome AF: 0.00511 AC: 5144 AN: 1006660 Hom.: 18 Cov.: 19 AF XY: 0.00528 AC XY: 1581 AN XY: 299170

Gnomad4 AFR exome AF: 0.000577

Gnomad4 AMR exome AF: 0.00223

Gnomad4 ASJ exome AF: 0.0237

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00200

Gnomad4 FIN exome AF: 0.00657

Gnomad4 NFE exome AF: 0.00519

Gnomad4 OTH exome AF: 0.00626

GnomAD4 genome AF: 0.00423 AC: 467 AN: 110305 Hom.: 0 Cov.: 23 AF XY: 0.00353 AC XY: 115 AN XY: 32593

Gnomad4 AFR AF: 0.000660

Gnomad4 AMR AF: 0.00344

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00272

Gnomad4 FIN AF: 0.00374

Gnomad4 NFE AF: 0.00596

Gnomad4 OTH AF: 0.00394

Alfa AF: 0.00909 Hom.: 62

Bravo AF: 0.00390

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	16
Dann	Benign	0.80
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs201770950; hg19: chrX-153214748;