NM_001350162.2:c.4252A>G

Variant names:

• chr8-30845915-T-C
• rs323346
• NM_001350162.2:c.4252A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350162.2(TEX15):​c.4252A>G​(p.Ile1418Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,612,788 control chromosomes in the GnomAD database, including 50,007 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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: 𝑓 0.34 (13300 hom., cov: 32)
  • Exomes 𝑓: 0.20 (36707 hom.)
• Consequence: TEX15 NM_001350162.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.6742902E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.4252A>G	p.Ile1418Val	missense_variant	Exon 8 of 11	ENST00000643185.2	NP_001337091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX15	ENST00000643185.2	c.4252A>G	p.Ile1418Val	missense_variant	Exon 8 of 11		NM_001350162.2	ENSP00000493555.1
TEX15	ENST00000256246.5	c.3103A>G	p.Ile1035Val	missense_variant	Exon 1 of 4	1		ENSP00000256246.2
TEX15	ENST00000638951.1	c.4264A>G	p.Ile1422Val	missense_variant	Exon 7 of 10	5		ENSP00000492713.1

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52044 AN: 151710 Hom.: 13270 Cov.: 32

Gnomad AFR AF: 0.716

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.100

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.313

GnomAD3 exomes AF: 0.251 AC: 62818 AN: 250134 Hom.: 11030 AF XY: 0.238 AC XY: 32197 AN XY: 135352

Gnomad AFR exome AF: 0.730

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0981

Gnomad SAS exome AF: 0.280

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.201 AC: 294118 AN: 1460960 Hom.: 36707 Cov.: 36 AF XY: 0.200 AC XY: 145575 AN XY: 726774

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.343 AC: 52137 AN: 151828 Hom.: 13300 Cov.: 32 AF XY: 0.343 AC XY: 25444 AN XY: 74242

Gnomad4 AFR AF: 0.716

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.101

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.312

Alfa AF: 0.195 Hom.: 9462

Bravo AF: 0.366

TwinsUK AF: 0.168 AC: 622

ALSPAC AF: 0.187 AC: 722

ESP6500AA AF: 0.694 AC: 3058

ESP6500EA AF: 0.171 AC: 1470

ExAC AF: 0.256 AC: 31124

Asia WGS AF: 0.255 AC: 888 AN: 3478

EpiCase AF: 0.162

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.78
DEOGEN2	Benign	0.049	.;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.61	T;T;T
MetaRNN	Benign	0.0000017	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	.;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.26	.;N;.
REVEL	Benign	0.036
Sift	Benign	0.62	.;T;.
Sift4G	Benign	1.0	.;T;.
Polyphen		0.037	.;B;.
Vest4		0.048
MPC		0.026
ClinPred		0.0017	T
GERP RS		0.22
Varity_R		0.031
gMVP		0.014

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: rs323346; hg19: chr8-30703431; COSMIC: COSV56351000;