X-55161146-C-G

Variant names:

• chrX-55161146-C-G
• rs146914917
• NM_001166701.4:c.11G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001166701.4(VCF2):​c.11G>C​(p.Cys4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000914 in 1,094,265 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C4Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: VCF2 NM_001166701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 0 publications found

Genes affected

VCF2 (HGNC:25085): (VCP nuclear cofactor family member 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.103613645).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCF2	NM_001166701.4	MANE Select	c.11G>C	p.Cys4Ser	missense	Exon 1 of 3	NP_001160173.1	A0A8I5KUH0
	VCF2	NM_001166699.2		c.11G>C	p.Cys4Ser	missense	Exon 1 of 4	NP_001160171.1	Q5XKR9-2
	VCF2	NM_001166700.2		c.11G>C	p.Cys4Ser	missense	Exon 1 of 3	NP_001160172.1	Q5XKR9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCF2	ENST00000685693.1	MANE Select	c.11G>C	p.Cys4Ser	missense	Exon 1 of 3	ENSP00000509111.1	A0A8I5KUH0
	VCF2	ENST00000332132.8	TSL:1	c.11G>C	p.Cys4Ser	missense	Exon 1 of 4	ENSP00000333394.4	Q5XKR9-2
	VCF2	ENST00000358460.8	TSL:1	c.11G>C	p.Cys4Ser	missense	Exon 1 of 4	ENSP00000364101.3	Q5XKR9-1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.14e-7 AC: 1 AN: 1094265 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 360183

African (AFR) AF: 0.00 AC: 0 AN: 26357

American (AMR) AF: 0.00 AC: 0 AN: 34874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19282

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30068

South Asian (SAS) AF: 0.00 AC: 0 AN: 53312

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840184

Other (OTH) AF: 0.00 AC: 0 AN: 45936

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.9
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.0
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.055
Sift	Benign	0.073	T
Sift4G	Benign	0.17	T
Polyphen		0.94	P
Vest4		0.30
MutPred		0.28		Gain of phosphorylation at C4 (P = 0.0017)
MVP		0.17
MPC		0.47
ClinPred		0.32	T
GERP RS		-0.92
PromoterAI		-0.072	Neutral
Varity_R		0.17
gMVP		0.054
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs146914917; hg19: chrX-55187579;