8-30874013-C-A

Variant names:

• chr8-30874013-C-A
• rs323376
• NM_001350162.2:c.302+924G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350162.2(TEX15):​c.302+924G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 152,034 control chromosomes in the GnomAD database, including 15,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (15065 hom., cov: 32)
• Consequence: TEX15 NM_001350162.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.302+924G>T		intron_variant	Intron 4 of 10	ENST00000643185.2	NP_001337091.1
TEX15	NR_146525.2	n.382+924G>T		intron_variant	Intron 3 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX15	ENST00000643185.2	c.302+924G>T		intron_variant	Intron 4 of 10		NM_001350162.2	ENSP00000493555.1
TEX15	ENST00000638951.1	c.314+924G>T		intron_variant	Intron 3 of 9	5		ENSP00000492713.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54519 AN: 151916 Hom.: 15027 Cov.: 32

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.0782

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.318

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.359 AC: 54623 AN: 152034 Hom.: 15065 Cov.: 32 AF XY: 0.358 AC XY: 26640 AN XY: 74324

African (AFR) AF: 0.769 AC: 31924 AN: 41494

American (AMR) AF: 0.344 AC: 5243 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 539 AN: 3466

East Asian (EAS) AF: 0.101 AC: 524 AN: 5176

South Asian (SAS) AF: 0.285 AC: 1374 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2396 AN: 10582

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11820 AN: 67948

Other (OTH) AF: 0.317 AC: 669 AN: 2110

Alfa AF: 0.190 Hom.: 1059

Bravo AF: 0.384

Asia WGS AF: 0.255 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.81
DANN	Benign	0.46
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs323376; hg19: chr8-30731529;