8-30836822-T-C

Variant names:

• chr8-30836822-T-C
• rs142159772
• NM_001350162.2:c.9462A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001350162.2(TEX15):​c.9462A>G​(p.Pro3154Pro) 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
• 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 -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 704 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	NM_001350162.2	MANE Select	c.9462A>G	p.Pro3154Pro	synonymous	Exon 10 of 11	NP_001337091.1	A0A2R8Y358

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	ENST00000643185.2	MANE Select	c.9462A>G	p.Pro3154Pro	synonymous	Exon 10 of 11	ENSP00000493555.1	A0A2R8Y358
	TEX15	ENST00000256246.5	TSL:1	c.8313A>G	p.Pro2771Pro	synonymous	Exon 3 of 4	ENSP00000256246.2	Q9BXT5
	TEX15	ENST00000638951.1	TSL:5	c.9474A>G	p.Pro3158Pro	synonymous	Exon 9 of 10	ENSP00000492713.1	A0A1W2PS94

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

GnomAD2 exomes AF: 0.00598 AC: 1470 AN: 245774 AF XY: 0.00621

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 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

African (AFR) AF: 0.000997 AC: 33 AN: 33108

American (AMR) AF: 0.00113 AC: 49 AN: 43500

Ashkenazi Jewish (ASJ) AF: 0.00113 AC: 29 AN: 25700

East Asian (EAS) AF: 0.00 AC: 0 AN: 39630

South Asian (SAS) AF: 0.00338 AC: 287 AN: 84906

European-Finnish (FIN) AF: 0.00826 AC: 440 AN: 53238

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5720

European-Non Finnish (NFE) AF: 0.00956 AC: 10604 AN: 1108848

Other (OTH) AF: 0.00463 AC: 278 AN: 60072

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

African (AFR) AF: 0.00123 AC: 51 AN: 41574

American (AMR) AF: 0.000784 AC: 12 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4818

European-Finnish (FIN) AF: 0.00688 AC: 73 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00803 AC: 546 AN: 68028

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.64
PhyloP100		0.74
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142159772; hg19: chr8-30694338;