8-30836822-T-C

Position:

• chr8-30836822-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001350162.2(TEX15):​c.9462A>G​(p.Pro3154=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 1,607,032 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0081 (67 hom.)
• Consequence: TEX15 NM_001350162.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.736

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 8-30836822-T-C is Benign according to our data. Variant chr8-30836822-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 788821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.736 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00462 (704/152310) while in subpopulation NFE AF= 0.00803 (546/68028). AF 95% confidence interval is 0.00747. There are 3 homozygotes in gnomad4. There are 328 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.9462A>G	p.Pro3154=	synonymous_variant	10/11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX15	ENST00000643185.2	c.9462A>G	p.Pro3154=	synonymous_variant	10/11		NM_001350162.2	ENSP00000493555	P4
TEX15	ENST00000256246.5	c.8313A>G	p.Pro2771=	synonymous_variant	3/4	1		ENSP00000256246
TEX15	ENST00000638951.1	c.9474A>G	p.Pro3158=	synonymous_variant	9/10	5		ENSP00000492713	A2

Frequencies

GnomAD3 genomes AF: 0.00463 AC: 705 AN: 152192 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00688

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00598 AC: 1470 AN: 245774 Hom.: 14 AF XY: 0.00621 AC XY: 825 AN XY: 132766

Gnomad AFR exome AF: 0.000741

Gnomad AMR exome AF: 0.00110

Gnomad ASJ exome AF: 0.000938

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00378

Gnomad FIN exome AF: 0.00805

Gnomad NFE exome AF: 0.00982

Gnomad OTH exome AF: 0.00538

GnomAD4 exome AF: 0.00807 AC: 11736 AN: 1454722 Hom.: 67 Cov.: 32 AF XY: 0.00792 AC XY: 5725 AN XY: 723160

Gnomad4 AFR exome AF: 0.000997

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.00113

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00338

Gnomad4 FIN exome AF: 0.00826

Gnomad4 NFE exome AF: 0.00956

Gnomad4 OTH exome AF: 0.00463

GnomAD4 genome AF: 0.00462 AC: 704 AN: 152310 Hom.: 3 Cov.: 32 AF XY: 0.00440 AC XY: 328 AN XY: 74480

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.00688

Gnomad4 NFE AF: 0.00803

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00628 Hom.: 4

Bravo AF: 0.00423

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00649

EpiControl AF: 0.00825

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Sep 12, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	TEX15: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs142159772; hg19: chr8-30694338;