rs323347

Variant names:

• chr8-30848708-A-G
• rs323347
• NM_001350162.2:c.1459T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350162.2(TEX15):​c.1459T>C​(p.Cys487Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,886 control chromosomes in the GnomAD database, including 53,021 homozygotes. 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: 𝑓 0.36 (14889 hom., cov: 32)
  • Exomes 𝑓: 0.20 (38132 hom.)
• Consequence: TEX15 NM_001350162.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.425
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1062657E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX15	NM_001350162.2	c.1459T>C	p.Cys487Arg	missense_variant	Exon 8 of 11	ENST00000643185.2	NP_001337091.1
TEX15	NR_146525.2	n.*19T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX15	ENST00000643185.2	c.1459T>C	p.Cys487Arg	missense_variant	Exon 8 of 11		NM_001350162.2	ENSP00000493555.1
TEX15	ENST00000256246.5	c.310T>C	p.Cys104Arg	missense_variant	Exon 1 of 4	1		ENSP00000256246.2
TEX15	ENST00000638951.1	c.1471T>C	p.Cys491Arg	missense_variant	Exon 7 of 10	5		ENSP00000492713.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54291 AN: 151976 Hom.: 14852 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.322

GnomAD2 exomes AF: 0.255 AC: 64172 AN: 251380 AF XY: 0.241

Gnomad AFR exome AF: 0.780

Gnomad AMR exome AF: 0.397

Gnomad ASJ exome AF: 0.150

Gnomad EAS exome AF: 0.0982

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.219

GnomAD4 exome AF: 0.203 AC: 296485 AN: 1461792 Hom.: 38132 Cov.: 36 AF XY: 0.202 AC XY: 146572 AN XY: 727194

African (AFR) AF: 0.781 AC: 26161 AN: 33480

American (AMR) AF: 0.393 AC: 17565 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 3882 AN: 26134

East Asian (EAS) AF: 0.105 AC: 4169 AN: 39696

South Asian (SAS) AF: 0.275 AC: 23733 AN: 86258

European-Finnish (FIN) AF: 0.218 AC: 11625 AN: 53416

Middle Eastern (MID) AF: 0.194 AC: 1121 AN: 5768

European-Non Finnish (NFE) AF: 0.175 AC: 194939 AN: 1111930

Other (OTH) AF: 0.220 AC: 13290 AN: 60388

GnomAD4 genome AF: 0.358 AC: 54395 AN: 152094 Hom.: 14889 Cov.: 32 AF XY: 0.357 AC XY: 26532 AN XY: 74354

African (AFR) AF: 0.764 AC: 31713 AN: 41496

American (AMR) AF: 0.343 AC: 5237 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 542 AN: 3468

East Asian (EAS) AF: 0.101 AC: 523 AN: 5172

South Asian (SAS) AF: 0.285 AC: 1371 AN: 4816

European-Finnish (FIN) AF: 0.226 AC: 2390 AN: 10562

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11809 AN: 67980

Other (OTH) AF: 0.321 AC: 676 AN: 2108

Alfa AF: 0.231 Hom.: 21462

Bravo AF: 0.382

TwinsUK AF: 0.168 AC: 622

ALSPAC AF: 0.188 AC: 723

ESP6500AA AF: 0.740 AC: 3261

ESP6500EA AF: 0.171 AC: 1470

ExAC AF: 0.261 AC: 31681

Asia WGS AF: 0.259 AC: 900 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	0.053
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.067
DANN	Benign	0.14
DEOGEN2	Benign	0.021	.;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0027	N
LIST_S2	Benign	0.12	T;T;T
MetaRNN	Benign	0.0000011	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	.;L;.
PhyloP100		-0.42
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.62	.;N;.
REVEL	Benign	0.014
Sift	Benign	0.71	.;T;.
Sift4G	Benign	0.52	.;T;.
Polyphen		0.0	.;B;.
Vest4		0.021
MPC		0.032
ClinPred		0.00072	T
GERP RS		-1.4
PromoterAI		0.021	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.083
gMVP		0.058
Mutation Taster		=100/0	polymorphism (auto)

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: rs323347; hg19: chr8-30706224; COSMIC: COSV56351021;