Variant X-8170042-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016378.3(VCX2):c.410G>A(p.Ser137Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 15)

Exomes 𝑓: 0.0000091 ( 0 hom. 6 hem. )

Failed GnomAD Quality Control

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.525

Variant links:

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]

VCX2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09569234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX2	NM_016378.3 linkuse as main transcript	c.410G>A	p.Ser137Asn	missense_variant	3/3	ENST00000317103.5	NP_057462.2
LOC107985675	XR_001755783.2 linkuse as main transcript	n.1915-58293C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
VCX2	ENST00000317103.5 linkuse as main transcript	c.410G>A	p.Ser137Asn	missense_variant	3/3	1	NM_016378.3	ENSP00000321309	P1
	ENST00000659022.1 linkuse as main transcript	n.972-58293C>T		intron_variant, non_coding_transcript_variant
	ENST00000649338.1 linkuse as main transcript	n.263-58293C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000550

AC:

AN:

181659

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67567

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000722

Gnomad SAS 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:

0.00000912

AC:

AN:

1096545

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

362865

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000594

Gnomad4 OTH exome

AF:

0.0000435

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 25, 2024

The c.410G>A (p.S137N) alteration is located in exon 3 (coding exon 2) of the VCX2 gene. This alteration results from a G to A substitution at nucleotide position 410, causing the serine (S) at amino acid position 137 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-1.1

CADD

Benign

1.6

DANN

Benign

0.80

DEOGEN2

Benign

0.0014

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.24

M_CAP

Benign

0.0012

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.69

REVEL

Benign

0.054

Sift

Benign

0.063

Sift4G

Benign

0.45

Polyphen

0.39

Vest4

0.15

MutPred

0.076

Loss of phosphorylation at S137 (P = 0.0123);

MVP

0.030

MPC

0.0092

ClinPred

0.084

GERP RS

0.19

Varity_R

0.17

gMVP

0.0013

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over