8-30836836-G-C

Variant names:

• chr8-30836836-G-C
• rs145745342
• NM_001350162.2:c.9448C>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.9448C>G​(p.Arg3150Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,852 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TEX15 NM_001350162.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=0.04737419).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.9448C>G	p.Arg3150Gly	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.9448C>G	p.Arg3150Gly	missense_variant	Exon 10 of 11		NM_001350162.2	ENSP00000493555.1
TEX15	ENST00000256246.5	c.8299C>G	p.Arg2767Gly	missense_variant	Exon 3 of 4	1		ENSP00000256246.2
TEX15	ENST00000638951.1	c.9460C>G	p.Arg3154Gly	missense_variant	Exon 9 of 10	5		ENSP00000492713.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1458852 Hom.: 0 Cov.: 32 AF XY: 0.00000965 AC XY: 7 AN XY: 725548

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: 0.00000990

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.3
DANN	Benign	0.75
DEOGEN2	Benign	0.023	.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.36	T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.0	.;N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.27	.;N;.
REVEL	Benign	0.022
Sift	Benign	0.36	.;T;.
Sift4G	Benign	0.30	.;T;.
Polyphen		0.0	.;B;.
Vest4		0.10
MutPred		0.30		.;Loss of stability (P = 0.0125);.;
MVP		0.14
MPC		0.028
ClinPred		0.057	T
GERP RS		-6.2
Varity_R		0.040
gMVP		0.072

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: rs145745342; hg19: chr8-30694352;