X-70623948-A-C

Position:

• chrX-70623948-A-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Moderate PM2 PP5_Moderate

The NM_031276.3(TEX11):​c.1751+2T>G variant causes a splice donor change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: TEX11 NM_031276.3 splice_donor
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.56

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 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.020158388 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant X-70623948-A-C is Pathogenic according to our data. Variant chrX-70623948-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 1210142.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.1751+2T>G		splice_donor_variant		ENST00000374333.7	NP_112566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX11	ENST00000374333.7	c.1751+2T>G		splice_donor_variant		1	NM_031276.3	ENSP00000363453	P2
TEX11	ENST00000344304.3	c.1796+2T>G		splice_donor_variant		5		ENSP00000340995	A2
TEX11	ENST00000374320.6	c.821+2T>G		splice_donor_variant		2		ENSP00000363440
TEX11	ENST00000395889.6	c.1796+2T>G		splice_donor_variant		2		ENSP00000379226	A2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 23

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
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Benign	0.96
FATHMM_MKL	Uncertain	0.86	D
MutationTaster	Benign	1.0	D;D;D;D
GERP RS		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.88
SpliceAI score (max)		0.96		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.96		Position offset: 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-69843798;