X-153949406-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005334.3(HCFC1):​c.6069-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000325 in 1,198,834 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 13 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000035 ( 0 hom. 13 hem. )

Consequence

HCFC1
NM_005334.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.146
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant X-153949406-A-G is Benign according to our data. Variant chrX-153949406-A-G is described in ClinVar as [Benign]. Clinvar id is 2716475.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 13 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HCFC1NM_005334.3 linkuse as main transcriptc.6069-20T>C intron_variant ENST00000310441.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HCFC1ENST00000310441.12 linkuse as main transcriptc.6069-20T>C intron_variant 1 NM_005334.3 P2P51610-1
HCFC1ENST00000369984.4 linkuse as main transcriptc.6204-20T>C intron_variant 5 A2
HCFC1ENST00000444191.5 linkuse as main transcriptc.1795-20T>C intron_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000902
AC:
1
AN:
110908
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33116
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000284
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000614
AC:
11
AN:
179138
Hom.:
0
AF XY:
0.0000458
AC XY:
3
AN XY:
65500
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000673
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000125
Gnomad OTH exome
AF:
0.000227
GnomAD4 exome
AF:
0.0000349
AC:
38
AN:
1087926
Hom.:
0
Cov.:
29
AF XY:
0.0000367
AC XY:
13
AN XY:
353920
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000862
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000120
Gnomad4 OTH exome
AF:
0.000240
GnomAD4 genome
AF:
0.00000902
AC:
1
AN:
110908
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
33116
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000284
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000718

ClinVar

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

Submissions by phenotype

Methylmalonic acidemia with homocystinuria, type cblX Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 29, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
1.4
DANN
Benign
0.32

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.

Other links and lift over

dbSNP: rs377160085; hg19: chrX-153214857; API