rs145972852

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001350162.2(TEX15):c.9368C>T(p.Ser3123Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00663 in 1,614,150 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0048 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 39 hom. )

Consequence

TEX15
NM_001350162.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.343

Publications

7 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0064715445).

BP6

Variant 8-30836916-G-A is Benign according to our data. Variant chr8-30836916-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 770379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00477 (727/152284) while in subpopulation NFE AF = 0.00682 (464/68014). AF 95% confidence interval is 0.00631. There are 7 homozygotes in GnomAd4. There are 356 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 727 Unknown,AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX15	NM_001350162.2	MANE Select	c.9368C>T	p.Ser3123Phe	missense	Exon 10 of 11	NP_001337091.1	A0A2R8Y358

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEX15	ENST00000643185.2	MANE Select	c.9368C>T	p.Ser3123Phe	missense	Exon 10 of 11	ENSP00000493555.1	A0A2R8Y358
TEX15	ENST00000256246.5	TSL:1	c.8219C>T	p.Ser2740Phe	missense	Exon 3 of 4	ENSP00000256246.2	Q9BXT5
TEX15	ENST00000638951.1	TSL:5	c.9380C>T	p.Ser3127Phe	missense	Exon 9 of 10	ENSP00000492713.1	A0A1W2PS94

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

727

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0120

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00682

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00529

AC:

1330

AN:

251364

AF XY:

0.00534

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00843

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.00718

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00682

AC:

9974

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

4693

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00111

AC:

AN:

33478

American (AMR)

AF:

0.00224

AC:

100

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00761

AC:

199

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0136

AC:

727

AN:

53414

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00770

AC:

8560

AN:

1112004

Other (OTH)

AF:

0.00575

AC:

347

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

550

1100

1649

2199

2749

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

324

648

972

1296

1620

<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

AF:

0.00477

AC:

727

AN:

152284

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

356

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00154

AC:

AN:

41562

American (AMR)

AF:

0.00242

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0120

AC:

127

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00682

AC:

464

AN:

68014

Other (OTH)

AF:

0.00473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00633

Hom.:

Bravo

AF:

0.00405

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00837

AC:

ExAC

AF:

0.00469

AC:

569

EpiCase

AF:

0.00649

EpiControl

AF:

0.00533

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

TEX15-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.065

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.54

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

0.34

PrimateAI

Benign

0.36

PROVEAN

Benign

0.47

REVEL

Benign

0.036

Sift

Benign

0.11

Sift4G

Benign

0.15

Polyphen

0.0

Vest4

0.25

MVP

0.17

MPC

0.025

ClinPred

0.0081

GERP RS

0.079

Varity_R

0.033

gMVP

0.086

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over