NM_001393662.1:c.216G>A

Variant names:

• chrX-7843611-G-A
• rs769730366
• NM_001393662.1:c.216G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001393662.1(VCX):​c.216G>A​(p.Ala72Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000063 (0 hom., 0 hem., cov: 10)
  • Exomes 𝑓: 0.00045 (11 hom. 49 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX NM_001393662.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.162
• Publications: 0 publications found

Genes affected

VCX (HGNC:12667): (variable charge X-linked) This gene belongs to the VCX/Y gene family, which has multiple members on both X and Y chromosomes, and all are expressed exclusively in male germ cells. The X-linked members are clustered on chromosome Xp22 and Y-linked members are two identical copies of the gene within a palindromic region on Yq11. The family members share a high degree of sequence identity, with the exception that a 30-bp unit is tandemly repeated in X-linked members but occurs only once in Y-linked members. The VCX gene cluster is polymorphic in terms of copy number; different individuals may have a different number of VCX genes. VCX/Y genes encode small and highly charged proteins of unknown function. The presence of a putative bipartite nuclear localization signal suggests that VCX/Y members are nuclear proteins. This gene contains 10 repeats of the 30-bp unit. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant X-7843611-G-A is Benign according to our data. Variant chrX-7843611-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2659918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.162 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393662.1. 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
	VCX	NM_001393662.1	MANE Select	c.216G>A	p.Ala72Ala	synonymous	Exon 2 of 2	NP_001380591.1	Q9H320
	VCX	NM_013452.3		c.216G>A	p.Ala72Ala	synonymous	Exon 3 of 3	NP_038480.2	Q9H320

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCX	ENST00000688183.1	MANE Select	c.216G>A	p.Ala72Ala	synonymous	Exon 2 of 2	ENSP00000509688.1	Q9H320
	VCX	ENST00000381059.7	TSL:1	c.216G>A	p.Ala72Ala	synonymous	Exon 3 of 3	ENSP00000370447.3	Q9H320
	VCX	ENST00000341408.6	TSL:5	c.216G>A	p.Ala72Ala	synonymous	Exon 2 of 3	ENSP00000344144.4	J3KNW2

Frequencies

GnomAD3 genomes AF: 0.0000625 AC: 4 AN: 63981 Hom.: 0 Cov.: 10

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000194

Gnomad ASJ AF: 0.000684

Gnomad EAS AF: 0.000442

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000324

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000423 AC: 62 AN: 146476 AF XY: 0.000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000326

Gnomad ASJ exome AF: 0.00193

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000771

Gnomad NFE exome AF: 0.000605

Gnomad OTH exome AF: 0.000806

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000448 AC: 467 AN: 1042752 Hom.: 11 Cov.: 83 AF XY: 0.000152 AC XY: 49 AN XY: 322074

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

African (AFR) AF: 0.0000774 AC: 2 AN: 25850

American (AMR) AF: 0.000331 AC: 11 AN: 33240

Ashkenazi Jewish (ASJ) AF: 0.00118 AC: 21 AN: 17803

East Asian (EAS) AF: 0.00 AC: 0 AN: 29657

South Asian (SAS) AF: 0.0000386 AC: 2 AN: 51844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36680

Middle Eastern (MID) AF: 0.000735 AC: 2 AN: 2722

European-Non Finnish (NFE) AF: 0.000506 AC: 405 AN: 801072

Other (OTH) AF: 0.000547 AC: 24 AN: 43884

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000625 AC: 4 AN: 63987 Hom.: 0 Cov.: 10 AF XY: 0.00 AC XY: 0 AN XY: 12065

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

African (AFR) AF: 0.00 AC: 0 AN: 18978

American (AMR) AF: 0.000195 AC: 1 AN: 5141

Ashkenazi Jewish (ASJ) AF: 0.000684 AC: 1 AN: 1462

East Asian (EAS) AF: 0.000445 AC: 1 AN: 2249

South Asian (SAS) AF: 0.00 AC: 0 AN: 1349

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2701

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 122

European-Non Finnish (NFE) AF: 0.0000324 AC: 1 AN: 30854

Other (OTH) AF: 0.00 AC: 0 AN: 757

⚠️ 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: 0.000831 Hom.: 6

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	-0.76
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		-0.16
PromoterAI		-0.052	Neutral
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: rs769730366; hg19: chrX-7811652;