X-70529952-C-A

Position:

• chrX-70529952-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_Moderate

The NM_031276.3(TEX11):​c.2568G>T​(p.Trp856Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TEX11 NM_031276.3 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.69

Genes affected

TEX11 (HGNC:11733): (testis expressed 11) This gene is X-linked and is expressed in only male germ cells. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.963
• PP5: Variant X-70529952-C-A is Pathogenic according to our data. Variant chrX-70529952-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 1210144.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3	c.2568G>T	p.Trp856Cys	missense_variant	29/30	ENST00000374333.7	NP_112566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX11	ENST00000374333.7	c.2568G>T	p.Trp856Cys	missense_variant	29/30	1	NM_031276.3	ENSP00000363453	P2
TEX11	ENST00000344304.3	c.2613G>T	p.Trp871Cys	missense_variant	28/29	5		ENSP00000340995	A2
TEX11	ENST00000395889.6	c.2613G>T	p.Trp871Cys	missense_variant	30/31	2		ENSP00000379226	A2
TEX11	ENST00000374320.6	c.1638G>T	p.Trp546Cys	missense_variant	18/19	2		ENSP00000363440

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Non-obstructive azoospermia Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Andrology Department, State Key Lab of Reproductive Medicine, Nanjing Medical University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.39
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.72	.;.;D;D
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	D;D;D;.
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.96	D;D;D;D
MetaSVM	Uncertain	-0.043	T
MutationAssessor	Uncertain	2.4	.;.;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-9.7	D;D;D;D
REVEL	Pathogenic	0.68
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;D;D
Vest4		0.96
MutPred		0.83		.;.;Loss of MoRF binding (P = 0.0135);Loss of MoRF binding (P = 0.0135);
MVP		0.66
MPC		1.3
ClinPred		1.0	D
GERP RS		4.3
Varity_R		0.94
gMVP		0.92

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69749802;