Genetic Variant NM_001350162.2:c.8083C>G (chr8-30842084-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001350162.2(TEX15):c.8083C>G(p.Arg2695Gly) 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 1,461,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.0000014 ( 0 hom. )

Consequence

TEX15
NM_001350162.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.14

Publications

0 publications found

Variant links:

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)

TEX15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20741004).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	NM_001350162.2	MANE Select	c.8083C>G	p.Arg2695Gly	missense	Exon 8 of 11	NP_001337091.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TEX15	ENST00000643185.2	MANE Select	c.8083C>G	p.Arg2695Gly	missense	Exon 8 of 11	ENSP00000493555.1
TEX15	ENST00000256246.5	TSL:1	c.6934C>G	p.Arg2312Gly	missense	Exon 1 of 4	ENSP00000256246.2
TEX15	ENST00000638951.1	TSL:5	c.8095C>G	p.Arg2699Gly	missense	Exon 7 of 10	ENSP00000492713.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461384

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33458

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111806

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.091

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.74

M_CAP

Benign

0.015

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

1.1

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-5.2

REVEL

Benign

0.087

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Polyphen

0.97

Vest4

0.38

MutPred

0.21

Gain of ubiquitination at K2310 (P = 0.0251)

MVP

0.31

MPC

0.20

ClinPred

0.87

GERP RS

3.6

Varity_R

0.22

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over