rs139945143

Variant names:

• chrX-8170151-G-C
• rs139945143
• NM_016378.3:c.301C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-8170151-G-C
• chrX-8170151-G-T
• chrX-8170151-G-A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016378.3(VCX2):​c.301C>G​(p.His101Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H101N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.000019 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: VCX2 NM_016378.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.905
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.050736338).

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.301C>G	p.His101Asp	missense	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.301C>G	p.His101Asp	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58184G>C		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58184G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 1 AN: 56162 Hom.: 0 Cov.: 8

Gnomad AFR AF: 0.00

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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000321

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 90793 AF XY: 0.00

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 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: 0.0000190 AC: 20 AN: 1054941 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 337033

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

African (AFR) AF: 0.0000394 AC: 1 AN: 25374

American (AMR) AF: 0.00 AC: 0 AN: 32634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18717

East Asian (EAS) AF: 0.0000340 AC: 1 AN: 29383

South Asian (SAS) AF: 0.00 AC: 0 AN: 51248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37082

Middle Eastern (MID) AF: 0.000354 AC: 1 AN: 2828

European-Non Finnish (NFE) AF: 0.0000197 AC: 16 AN: 813346

Other (OTH) AF: 0.0000226 AC: 1 AN: 44329

⚠️ 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: 0.0000178 AC: 1 AN: 56162 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6516

⚠️ 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: 13403

American (AMR) AF: 0.00 AC: 0 AN: 4129

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1694

East Asian (EAS) AF: 0.00 AC: 0 AN: 1369

South Asian (SAS) AF: 0.00 AC: 0 AN: 853

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2509

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.0000321 AC: 1 AN: 31136

Other (OTH) AF: 0.00 AC: 0 AN: 610

⚠️ 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.

ExAC AF: 0.000259 AC: 26

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.34
DANN	Benign	0.50
DEOGEN2	Benign	0.0072	T
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.00090	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.91
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.11
Sift	Benign	0.59	T
Sift4G	Benign	0.46	T
Polyphen		0.60	P
Vest4		0.25
MutPred		0.068		Gain of relative solvent accessibility (P = 0.0098)
MVP		0.055
MPC		0.0087
ClinPred		0.25	T
GERP RS		0.046
Varity_R		0.17
gMVP		0.0017
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: rs139945143; hg19: chrX-8138192;