X-153952697-G-C

Variant names:

• chrX-153952697-G-C
• NM_005334.3:c.4759C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005334.3(HCFC1):​c.4759C>G​(p.Leu1587Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000913 in 1,095,599 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: HCFC1 NM_005334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.26

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23304486).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HCFC1	NM_005334.3	c.4759C>G	p.Leu1587Val	missense_variant	Exon 19 of 26	ENST00000310441.12	NP_005325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HCFC1	ENST00000310441.12	c.4759C>G	p.Leu1587Val	missense_variant	Exon 19 of 26	1	NM_005334.3	ENSP00000309555.7
HCFC1	ENST00000369984.4	c.4891C>G	p.Leu1631Val	missense_variant	Exon 19 of 26	5		ENSP00000359001.4
HCFC1	ENST00000444191.5	c.481C>G	p.Leu161Val	missense_variant	Exon 3 of 10	5		ENSP00000399589.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095599 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 361675

Gnomad4 AFR exome AF: 0.0000379

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.096
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.26	T;T
Polyphen		0.73	P;.
Vest4		0.21
MutPred		0.13		Loss of glycosylation at S1586 (P = 0.1089);.;
MVP		0.69
MPC		1.4
ClinPred		0.96	D
GERP RS		4.9
Varity_R		0.73
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-153218148;