8-30837159-G-C

Variant names:

• chr8-30837159-G-C
• rs1807323191
• NM_001350162.2:c.9125C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350162.2(TEX15):​c.9125C>G​(p.Ser3042Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TEX15 NM_001350162.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0280

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05208665).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.9125C>G	p.Ser3042Cys	missense_variant	Exon 10 of 11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX15	ENST00000643185.2	c.9125C>G	p.Ser3042Cys	missense_variant	Exon 10 of 11		NM_001350162.2	ENSP00000493555.1
TEX15	ENST00000256246.5	c.7976C>G	p.Ser2659Cys	missense_variant	Exon 3 of 4	1		ENSP00000256246.2
TEX15	ENST00000638951.1	c.9137C>G	p.Ser3046Cys	missense_variant	Exon 9 of 10	5		ENSP00000492713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461790 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727208

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.7976C>G (p.S2659C) alteration is located in exon 3 (coding exon 3) of the TEX15 gene. This alteration results from a C to G substitution at nucleotide position 7976, causing the serine (S) at amino acid position 2659 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.068	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.052	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.27	.;N;.
REVEL	Benign	0.024
Sift	Uncertain	0.025	.;D;.
Sift4G	Uncertain	0.015	.;D;.
Polyphen		0.0030	.;B;.
Vest4		0.26
MutPred		0.43		.;Loss of disorder (P = 0.0975);.;
MVP		0.17
MPC		0.024
ClinPred		0.093	T
GERP RS		1.9
Varity_R		0.058
gMVP		0.20

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: rs1807323191; hg19: chr8-30694675;