Variant X-153949297-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.49

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 115 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCFC1	NM_005334.3 linkuse as main transcript	c.*50G>A		3_prime_UTR_variant	26/26	ENST00000310441.12	NP_005325.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCFC1	ENST00000310441.12 linkuse as main transcript	c.*50G>A	3_prime_UTR_variant	26/26	1	NM_005334.3	ENSP00000309555	P2	P51610-1
HCFC1	ENST00000369984.4 linkuse as main transcript	c.*50G>A	3_prime_UTR_variant	26/26	5		ENSP00000359001	A2
HCFC1	ENST00000444191.5 linkuse as main transcript	c.*50G>A	3_prime_UTR_variant	10/10	5		ENSP00000399589

Frequencies

GnomAD3 genomes

AF:

0.00424

AC:

468

AN:

110258

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

115

AN XY:

32536

show subpopulations

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.:

AF XY:

0.00509

AC XY:

284

AN XY:

55788

show subpopulations

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.:

Cov.:

AF XY:

0.00528

AC XY:

1581

AN XY:

299170

show subpopulations

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.:

Cov.:

AF XY:

0.00353

AC XY:

115

AN XY:

32593

show subpopulations

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.:

Bravo

AF:

0.00390

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 25, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over