chrX-8170143-G-T

Variant names:

• chrX-8170143-G-T
• rs778640992
• NM_016378.3:c.309C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016378.3(VCX2):​c.309C>A​(p.Pro103Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000369 in 1,054,007 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00035 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.00037 (0 hom. 33 hem.)
• Consequence: VCX2 NM_016378.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.42
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.12).
• BP6: Variant X-8170143-G-T is Benign according to our data. Variant chrX-8170143-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659926.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 33 gene

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.309C>A	p.Pro103Pro	synonymous	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.309C>A	p.Pro103Pro	synonymous	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58192G>T		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58192G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000349 AC: 20 AN: 57348 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.000438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000387

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000411

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000519 AC: 47 AN: 90592 AF XY: 0.000145

Gnomad AFR exome AF: 0.00103

Gnomad AMR exome AF: 0.0000741

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000274

Gnomad FIN exome AF: 0.000385

Gnomad NFE exome AF: 0.000807

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000370 AC: 369 AN: 996669 Hom.: 0 Cov.: 28 AF XY: 0.000109 AC XY: 33 AN XY: 303953

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000703 AC: 17 AN: 24184

American (AMR) AF: 0.000128 AC: 4 AN: 31162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18081

East Asian (EAS) AF: 0.000207 AC: 6 AN: 28942

South Asian (SAS) AF: 0.000205 AC: 10 AN: 48685

European-Finnish (FIN) AF: 0.000853 AC: 31 AN: 36363

Middle Eastern (MID) AF: 0.000370 AC: 1 AN: 2703

European-Non Finnish (NFE) AF: 0.000370 AC: 283 AN: 764085

Other (OTH) AF: 0.000400 AC: 17 AN: 42464

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000349 AC: 20 AN: 57338 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6748

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000437 AC: 6 AN: 13719

American (AMR) AF: 0.00 AC: 0 AN: 4260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1708

East Asian (EAS) AF: 0.00 AC: 0 AN: 1440

South Asian (SAS) AF: 0.00 AC: 0 AN: 865

European-Finnish (FIN) AF: 0.000387 AC: 1 AN: 2584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 87

European-Non Finnish (NFE) AF: 0.000411 AC: 13 AN: 31647

Other (OTH) AF: 0.00 AC: 0 AN: 642

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.56
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs778640992; hg19: chrX-8138184;