X-8170078-G-T

Variant names:

• chrX-8170078-G-T
• rs367654337
• NM_016378.3:c.374C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016378.3(VCX2):​c.374C>A​(p.Thr125Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 15)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.07

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06332198).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCX2	NM_016378.3	c.374C>A	p.Thr125Asn	missense_variant	Exon 3 of 3	ENST00000317103.5	NP_057462.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCX2	ENST00000317103.5	c.374C>A	p.Thr125Asn	missense_variant	Exon 3 of 3	1	NM_016378.3	ENSP00000321309.4
ENSG00000285679	ENST00000649338.1	n.263-58257G>T		intron_variant	Intron 3 of 4
ENSG00000285679	ENST00000659022.1	n.972-58257G>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 15

GnomAD3 exomes AF: 0.00000550 AC: 1 AN: 181751 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67645

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000124

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.12e-7 AC: 1 AN: 1096262 Hom.: 0 Cov.: 76 AF XY: 0.00000276 AC XY: 1 AN XY: 362660

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 15

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.061
DANN	Benign	0.39
DEOGEN2	Benign	0.0020	T
FATHMM_MKL	Benign	0.00042	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.059
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.010	D
Vest4		0.14
MutPred		0.20		Loss of sheet (P = 0.0054);
MVP		0.088
MPC		0.0090
ClinPred		0.048	T
Varity_R		0.21
gMVP		0.0062

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

Publications

LitVar

Other links and lift over

dbSNP: rs367654337; hg19: chrX-8138119;