chrX-55146214-G-A

Variant names:

• chrX-55146214-G-A
• rs866839768
• NM_001166701.4:c.218C>T

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.218C>T​(p.Pro73Leu) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: VCF2 NM_001166701.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.840
• Publications: 2 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=0.054038584).

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.218C>T	p.Pro73Leu	missense	Exon 3 of 3	NP_001160173.1	A0A8I5KUH0
	VCF2	NM_001166699.2		c.221C>T	p.Pro74Leu	missense	Exon 3 of 4	NP_001160171.1	Q5XKR9-2
	VCF2	NM_001166700.2		c.221C>T	p.Pro74Leu	missense	Exon 3 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.218C>T	p.Pro73Leu	missense	Exon 3 of 3	ENSP00000509111.1	A0A8I5KUH0
	VCF2	ENST00000332132.8	TSL:1	c.221C>T	p.Pro74Leu	missense	Exon 3 of 4	ENSP00000333394.4	Q5XKR9-2
	VCF2	ENST00000358460.8	TSL:1	c.218C>T	p.Pro73Leu	missense	Exon 3 of 4	ENSP00000364101.3	Q5XKR9-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.78
DEOGEN2	Benign	0.014	T
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.84
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.035
Sift	Benign	0.32	T
Sift4G	Benign	0.12	T
Polyphen		0.94	P
Vest4		0.14
MutPred		0.34		Gain of sheet (P = 0.0266)
MVP		0.092
MPC		0.46
ClinPred		0.058	T
GERP RS		-0.40
Varity_R		0.041
gMVP		0.16
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs866839768; hg19: chrX-55172647; COSMIC: COSV100146088; COSMIC: COSV100146088;