rs1051152

Positions:

• chrX-153954909-A-C
• chrX-153954909-A-G
• chrX-153954909-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Strong

The NM_005334.3(HCFC1):​c.3490T>G​(p.Ser1164Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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: 24)
• Consequence: HCFC1 NM_005334.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.650

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HCFC1. . Gene score misZ 5.6341 (greater than the threshold 3.09). GenCC has associacion of gene with X-linked intellectual disability, non-syndromic X-linked intellectual disability, methylmalonic acidemia with homocystinuria, type cblX.
• BP4: Computational evidence support a benign effect (MetaRNN=0.045206547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCFC1	NM_005334.3	c.3490T>G	p.Ser1164Ala	missense_variant	17/26	ENST00000310441.12	NP_005325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCFC1	ENST00000310441.12	c.3490T>G	p.Ser1164Ala	missense_variant	17/26	1	NM_005334.3	ENSP00000309555	P2
HCFC1	ENST00000369984.4	c.3490T>G	p.Ser1164Ala	missense_variant	17/26	5		ENSP00000359001	A2

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.075	T;T
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.30	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.045	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.34	N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.034
Sift	Benign	0.17	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.0	B;.
Vest4		0.068
MutPred		0.15		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.22
MPC		0.45
ClinPred		0.11	T
GERP RS		-0.34
Varity_R		0.070
gMVP		0.25

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

Other links and lift over

dbSNP: rs1051152; hg19: chrX-153220360;