NM_016378.3:c.307C>A

Variant names:

• chrX-8170145-G-T
• rs772176238
• NM_016378.3:c.307C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016378.3(VCX2):​c.307C>A​(p.Pro103Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P103P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000029 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.236
• Publications: 0 publications found

Genes affected

VCX2 (HGNC:18158): (variable charge X-linked 2) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes that are expressed exclusively in male germ cells. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. This gene contains two copies of a 30 nt tandem repeat. Deletion of a nearby member of this family was implicated in cognitive disability. [provided by RefSeq, Feb 2015]

ENSG00000285679 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.14845961).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016378.3. 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
	VCX2	NM_016378.3	MANE Select	c.307C>A	p.Pro103Thr	missense	Exon 3 of 3	NP_057462.2	Q9H322

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX2	ENST00000317103.5	TSL:1 MANE Select	c.307C>A	p.Pro103Thr	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58190G>T		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58190G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD2 exomes AF: 0.00000746 AC: 1 AN: 134001 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000289 AC: 3 AN: 1037709 Hom.: 0 Cov.: 29 AF XY: 0.00000316 AC XY: 1 AN XY: 316853

African (AFR) AF: 0.00 AC: 0 AN: 25319

American (AMR) AF: 0.0000621 AC: 2 AN: 32216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18471

East Asian (EAS) AF: 0.00 AC: 0 AN: 29304

South Asian (SAS) AF: 0.00 AC: 0 AN: 50032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2793

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 797365

Other (OTH) AF: 0.00 AC: 0 AN: 43969

GnomAD4 genome Cov.: 8

Alfa AF: 0.00 Hom.: 0

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	0.10
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.6
DANN	Benign	0.82
DEOGEN2	Benign	0.031	T
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.24
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.062
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.94	P
Vest4		0.14
MutPred		0.14		Gain of phosphorylation at P103 (P = 0.0567)
MVP		0.088
MPC		0.0090
ClinPred		0.62	D
GERP RS		0.046
Varity_R		0.48
gMVP		0.0039
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: rs772176238; hg19: chrX-8138186;