Variant X-8170129-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_016378.3(VCX2):c.323G>C(p.Ser108Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 15668 hom., 3216 hem., cov: 9)

Exomes 𝑓: 0.77 ( 162123 hom. 217551 hem. )

Failed GnomAD Quality Control

Consequence

VCX2
NM_016378.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.27

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 Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.512189E-5).

BP6

Variant X-8170129-C-G is Benign according to our data. Variant chrX-8170129-C-G is described in ClinVar as [Benign]. Clinvar id is 769172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCX2	NM_016378.3 linkuse as main transcript	c.323G>C	p.Ser108Thr	missense_variant	3/3	ENST00000317103.5	NP_057462.2
LOC107985675	XR_001755783.2 linkuse as main transcript	n.1915-58206C>G		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.323G>C	p.Ser108Thr	missense_variant	3/3	1	NM_016378.3	ENSP00000321309	P1
	ENST00000659022.1 linkuse as main transcript	n.972-58206C>G		intron_variant, non_coding_transcript_variant
	ENST00000649338.1 linkuse as main transcript	n.263-58206C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.723

AC:

43982

AN:

60821

Hom.:

15672

Cov.:

AF XY:

0.425

AC XY:

3208

AN XY:

7555

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.772

Gnomad AMR

AF:

0.800

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.916

Gnomad SAS

AF:

0.603

Gnomad FIN

AF:

0.584

Gnomad MID

AF:

0.733

Gnomad NFE

AF:

0.708

Gnomad OTH

AF:

0.728

GnomAD3 exomes

AF:

0.771

AC:

94641

AN:

122744

Hom.:

27558

AF XY:

0.715

AC XY:

32163

AN XY:

44958

show subpopulations

Gnomad AFR exome

AF:

0.780

Gnomad AMR exome

AF:

0.875

Gnomad ASJ exome

AF:

0.703

Gnomad EAS exome

AF:

0.937

Gnomad SAS exome

AF:

0.737

Gnomad FIN exome

AF:

0.710

Gnomad NFE exome

AF:

0.726

Gnomad OTH exome

AF:

0.754

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.769

AC:

593506

AN:

772169

Hom.:

162123

Cov.:

AF XY:

0.752

AC XY:

217551

AN XY:

289395

show subpopulations

Gnomad4 AFR exome

AF:

0.787

Gnomad4 AMR exome

AF:

0.852

Gnomad4 ASJ exome

AF:

0.712

Gnomad4 EAS exome

AF:

0.956

Gnomad4 SAS exome

AF:

0.774

Gnomad4 FIN exome

AF:

0.746

Gnomad4 NFE exome

AF:

0.757

Gnomad4 OTH exome

AF:

0.780

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.723

AC:

43979

AN:

60815

Hom.:

15668

Cov.:

AF XY:

0.425

AC XY:

3216

AN XY:

7567

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.800

Gnomad4 ASJ

AF:

0.665

Gnomad4 EAS

AF:

0.915

Gnomad4 SAS

AF:

0.603

Gnomad4 FIN

AF:

0.584

Gnomad4 NFE

AF:

0.708

Gnomad4 OTH

AF:

0.723

Alfa

AF:

0.660

Hom.:

4111

ExAC

AF:

0.745

AC:

87518

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.98

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.22

DANN

Benign

0.076

DEOGEN2

Benign

0.00064

FATHMM_MKL

Benign

0.000040

LIST_S2

Benign

0.38

MetaRNN

Benign

0.000065

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.93

REVEL

Benign

0.018

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.091

MPC

0.0092

ClinPred

0.00061

GERP RS

0.046

Varity_R

0.14

gMVP

0.0018

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