X-55159199-C-T

Variant names:

• chrX-55159199-C-T
• rs758818648
• NM_001166701.4:c.50G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001166701.4(VCF2):​c.50G>A​(p.Gly17Asp) 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. 15/21 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. G17V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 23)
• Consequence: VCF2 NM_001166701.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 7 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.020214349).

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.50G>A	p.Gly17Asp	missense	Exon 2 of 3	NP_001160173.1	A0A8I5KUH0
	VCF2	NM_001166699.2		c.50G>A	p.Gly17Asp	missense	Exon 2 of 4	NP_001160171.1	Q5XKR9-2
	VCF2	NM_001166700.2		c.50G>A	p.Gly17Asp	missense	Exon 2 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.50G>A	p.Gly17Asp	missense	Exon 2 of 3	ENSP00000509111.1	A0A8I5KUH0
	VCF2	ENST00000332132.8	TSL:1	c.50G>A	p.Gly17Asp	missense	Exon 2 of 4	ENSP00000333394.4	Q5XKR9-2
	VCF2	ENST00000358460.8	TSL:1	c.50G>A	p.Gly17Asp	missense	Exon 2 of 4	ENSP00000364101.3	Q5XKR9-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.018
DANN	Benign	0.19
DEOGEN2	Benign	0.0060	T
FATHMM_MKL	Benign	0.00040	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.9	N
PhyloP100		0.26
PrimateAI	Benign	0.42	T
PROVEAN	Benign	3.9	N
REVEL	Benign	0.027
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.15		Loss of MoRF binding (P = 0.0561)
MVP		0.030
MPC		0.10
ClinPred		0.029	T
GERP RS		-1.3
Varity_R		0.053
gMVP		0.048
Mutation Taster		=99/1	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: rs758818648; hg19: chrX-55185632;