rs864309485

Variant names:

• chr8-30846888-A-C
• rs864309485
• NM_001350162.2:c.3279T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-30846888-A-C
• chr8-30846888-A-G
• chr8-30846888-A-T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_001350162.2(TEX15):​c.3279T>G​(p.Tyr1093*) 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
• Publications: 4 publications found

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]

TEX15 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 25

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Pathogenic. The variant received 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 VariationId is 190036.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350162.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	NM_001350162.2	MANE Select	c.3279T>G	p.Tyr1093*	stop_gained	Exon 8 of 11	NP_001337091.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	ENST00000643185.2	MANE Select	c.3279T>G	p.Tyr1093*	stop_gained	Exon 8 of 11	ENSP00000493555.1
	TEX15	ENST00000256246.5	TSL:1	c.2130T>G	p.Tyr710*	stop_gained	Exon 1 of 4	ENSP00000256246.2
	TEX15	ENST00000638951.1	TSL:5	c.3291T>G	p.Tyr1097*	stop_gained	Exon 7 of 10	ENSP00000492713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Oligosynaptic infertility (1)
1	-	-	Spermatogenic failure 25 (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		0.49
Vest4		0.29
GERP RS		-0.83
Mutation Taster		=13/187	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs864309485; hg19: chr8-30704404;