X-153949570-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005334.3(HCFC1):​c.6051C>T​(p.Pro2017=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000911 in 1,097,250 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000091 ( 0 hom. 6 hem. )

Consequence

HCFC1
NM_005334.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.771
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant X-153949570-G-A is Benign according to our data. Variant chrX-153949570-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2831510.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.771 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 6 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HCFC1NM_005334.3 linkuse as main transcriptc.6051C>T p.Pro2017= synonymous_variant 25/26 ENST00000310441.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HCFC1ENST00000310441.12 linkuse as main transcriptc.6051C>T p.Pro2017= synonymous_variant 25/261 NM_005334.3 P2P51610-1
HCFC1ENST00000369984.4 linkuse as main transcriptc.6186C>T p.Pro2062= synonymous_variant 25/265 A2
HCFC1ENST00000444191.5 linkuse as main transcriptc.1779C>T p.Pro593= synonymous_variant 9/105

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
0.00000911
AC:
10
AN:
1097250
Hom.:
0
Cov.:
30
AF XY:
0.0000165
AC XY:
6
AN XY:
362652
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000119
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Methylmalonic acidemia with homocystinuria, type cblX Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
CADD
Benign
7.6
DANN
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153215021; API