rs864309485

chr8-30846888-A-Cchr8-30846888-A-G

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001350162.2(TEX15):c.3279T>G(p.Tyr1093Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. 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 (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TEX15 NM_001350162.2 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.487

Genes affected

TEX15 (HGNC:11738): (testis expressed 15, meiosis and synapsis associated) This gene encodes a protein that is required for DNA double-strand break repair, chromosome synapsis, and meiotic recombination in spermatocytes. Male mice with a knockout of the orthologous gene are viable but sterile. Loss-of-function mutations in the orthologous mouse gene cause early meiotic arrest in spermatocytes, before the mid-pachytene stage. Naturally occurring mutations in this gene are associated with nonobstructive azoospermia. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-30846888-A-C is Pathogenic according to our data. Variant chr8-30846888-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 190036.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX15	NM_001350162.2	c.3279T>G	p.Tyr1093Ter	stop_gained	8/11	ENST00000643185.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX15	ENST00000643185.2	c.3279T>G	p.Tyr1093Ter	stop_gained	8/11		NM_001350162.2	P4
TEX15	ENST00000256246.5	c.2130T>G	p.Tyr710Ter	stop_gained	1/4	1
TEX15	ENST00000638951.1	c.3291T>G	p.Tyr1097Ter	stop_gained	7/10	5		A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

Submissions by phenotype

Oligosynaptic infertility Pathogenic:1

Pathogenic, criteria provided, single submitter

research

Research lab, Institute of Genetics and Molecular and Cellular Biology

-

autosomal recessive form of spermatogenic failure associated with defects in meiosis -

Spermatogenic failure 25 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 01, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Uncertain	0.010
Cadd	Pathogenic	28
Dann	Benign	0.96
Eigen	Benign	-0.096
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.28	N
MutationTaster	Benign	1.0	A
Vest4		0.29
GERP RS		-0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs864309485; hg19: chr8-30704404;