X-55146163-C-A

Variant names:

• chrX-55146163-C-A
• rs749664168
• NM_001166701.4:c.269G>T

Variant summary

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

The NM_001166701.4(VCF2):​c.269G>T​(p.Gly90Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 11/18 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. G90A) 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: 2.61
• Publications: 4 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.269G>T	p.Gly90Val	missense	Exon 3 of 3	NP_001160173.1	A0A8I5KUH0
	VCF2	NM_001166700.2		c.272G>T	p.Gly91Val	missense	Exon 3 of 3	NP_001160172.1	Q5XKR9-3
	VCF2	NM_001166703.2		c.266G>T	p.Gly89Val	missense	Exon 3 of 3	NP_001160175.1	Q5XKR9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCF2	ENST00000685693.1	MANE Select	c.269G>T	p.Gly90Val	missense	Exon 3 of 3	ENSP00000509111.1	A0A8I5KUH0
	VCF2	ENST00000472571.2	TSL:1	c.*135G>T		3_prime_UTR	Exon 3 of 3	ENSP00000420895.1	Q5XKR9-5
	VCF2	ENST00000332132.8	TSL:1	c.254+18G>T		intron	N/A	ENSP00000333394.4	Q5XKR9-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Uncertain	0.99
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-1.0	T
PhyloP100		2.6
PROVEAN	Pathogenic	-7.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.71
MutPred		0.50		Gain of sheet (P = 0.0149)
MVP		0.18
MPC		0.17
ClinPred		0.95	D
GERP RS		1.6
gMVP		0.38
Mutation Taster		=94/6	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: rs749664168; hg19: chrX-55172596;