rs145994467

Variant names:

• chrX-8170149-G-C
• rs145994467
• NM_016378.3:c.303C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-8170149-G-C
• chrX-8170149-G-T
• chrX-8170149-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.303C>G​(p.His101Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. 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 0.0 (0 hom., 0 hem., cov: 8)
  • Exomes 𝑓: 0.000022 (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: -1.55
• Publications: 1 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=0.05393651).

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.303C>G	p.His101Gln	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.303C>G	p.His101Gln	missense	Exon 3 of 3	ENSP00000321309.4	Q9H322
	ENSG00000285679	ENST00000649338.1		n.263-58186G>C		intron	N/A
	ENSG00000285679	ENST00000659022.1		n.972-58186G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 56115 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 1 AN: 89764 AF XY: 0.0000364

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: 0.0000254

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000220 AC: 23 AN: 1043248 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 329404

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

African (AFR) AF: 0.0000399 AC: 1 AN: 25091

American (AMR) AF: 0.00 AC: 0 AN: 32361

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18572

East Asian (EAS) AF: 0.000102 AC: 3 AN: 29287

South Asian (SAS) AF: 0.0000197 AC: 1 AN: 50703

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36948

Middle Eastern (MID) AF: 0.000355 AC: 1 AN: 2813

European-Non Finnish (NFE) AF: 0.0000212 AC: 17 AN: 803526

Other (OTH) AF: 0.00 AC: 0 AN: 43947

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000216382), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 56108 Hom.: 0 Cov.: 8 AF XY: 0.00 AC XY: 0 AN XY: 6550

African (AFR) AF: 0.00 AC: 0 AN: 13386

American (AMR) AF: 0.00 AC: 0 AN: 4158

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1695

East Asian (EAS) AF: 0.00 AC: 0 AN: 1362

South Asian (SAS) AF: 0.00 AC: 0 AN: 850

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 81

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31076

Other (OTH) AF: 0.00 AC: 0 AN: 629

ESP6500AA AF: 0.00319 AC: 12

ESP6500EA AF: 0.00151 AC: 10

ExAC AF: 0.000124 AC: 12

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	0.20
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.29
DANN	Benign	0.42
DEOGEN2	Benign	0.0026	T
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.13
Sift	Benign	0.28	T
Sift4G	Benign	0.23	T
Polyphen		0.79	P
Vest4		0.10
MutPred		0.052		Gain of solvent accessibility (P = 0.0155)
MVP		0.048
MPC		0.0091
ClinPred		0.11	T
GERP RS		0.046
Varity_R		0.18
gMVP		0.0018
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: rs145994467; hg19: chrX-8138190;