chrX-153949391-G-A

Variant summary

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

The NM_005334.3(HCFC1):​c.6069-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000699 in 1,202,368 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 3 hem., cov: 23)
Exomes 𝑓: 0.000072 ( 0 hom. 37 hem. )

Consequence

HCFC1
NM_005334.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0003615
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70
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=-0.74).
BP6
Variant X-153949391-G-A is Benign according to our data. Variant chrX-153949391-G-A is described in ClinVar as [Benign]. Clinvar id is 1576392.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HCFC1NM_005334.3 linkuse as main transcriptc.6069-5C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000310441.12

Ensembl

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

Frequencies

GnomAD3 genomes
AF:
0.0000451
AC:
5
AN:
110914
Hom.:
0
Cov.:
23
AF XY:
0.0000906
AC XY:
3
AN XY:
33110
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:
0.00
Gnomad SAS
AF:
0.00192
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000144
AC:
26
AN:
180058
Hom.:
0
AF XY:
0.000241
AC XY:
16
AN XY:
66300
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00137
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000724
AC:
79
AN:
1091454
Hom.:
0
Cov.:
29
AF XY:
0.000104
AC XY:
37
AN XY:
357346
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:
0.00141
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000654
GnomAD4 genome
AF:
0.0000451
AC:
5
AN:
110914
Hom.:
0
Cov.:
23
AF XY:
0.0000906
AC XY:
3
AN XY:
33110
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00192
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000187
Hom.:
0
Bravo
AF:
0.0000227

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 testingInvitaeJan 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
9.7
DANN
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00036
dbscSNV1_RF
Benign
0.014
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: rs782321258; hg19: chrX-153214842; API