Genetic Variant NM_031276.3:c.405C>T (chrX-70853248-G-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_031276.3(TEX11):c.405C>T(p.Ala135Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00334 in 1,207,420 control chromosomes in the GnomAD database, including 6 homozygotes. There are 1,276 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 2 hom., 77 hem., cov: 23)

Exomes 𝑓: 0.0034 ( 4 hom. 1199 hem. )

Consequence

TEX11
NM_031276.3 splice_region, synonymous

Scores

Splicing: ADA: 0.0001811

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: -0.286

Publications

6 publications found

Variant links:

Genes affected

TEX11 (HGNC:11733): (testis expressed 11) This gene is X-linked and is expressed in only male germ cells. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TEX11 Gene-Disease associations (from GenCC):

spermatogenic failure, X-linked, 2
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TEX11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant X-70853248-G-A is Benign according to our data. Variant chrX-70853248-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 192381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.286 with no splicing effect.

BS2

High AC in GnomAd4 at 263 XL,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031276.3. 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
	TEX11	NM_031276.3	MANE Select	c.405C>T	p.Ala135Ala	splice_region synonymous	Exon 6 of 30	NP_112566.2	Q8IYF3-3
	TEX11	NM_001003811.2		c.450C>T	p.Ala150Ala	splice_region synonymous	Exon 7 of 31	NP_001003811.1	Q8IYF3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TEX11	ENST00000374333.7	TSL:1 MANE Select	c.405C>T	p.Ala135Ala	splice_region synonymous	Exon 6 of 30	ENSP00000363453.2	Q8IYF3-3
TEX11	ENST00000344304.3	TSL:5	c.450C>T	p.Ala150Ala	splice_region synonymous	Exon 5 of 29	ENSP00000340995.3	Q8IYF3-1
TEX11	ENST00000395889.6	TSL:2	c.450C>T	p.Ala150Ala	splice_region synonymous	Exon 7 of 31	ENSP00000379226.2	Q8IYF3-1

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

263

AN:

111875

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000715

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000479

Gnomad ASJ

AF:

0.00226

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000498

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00425

Gnomad OTH

AF:

0.000667

GnomAD2 exomes

AF:

0.00192

AC:

351

AN:

182786

AF XY:

0.00172

show subpopulations

Gnomad AFR exome

AF:

0.000685

Gnomad AMR exome

AF:

0.000256

Gnomad ASJ exome

AF:

0.00321

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000751

Gnomad NFE exome

AF:

0.00359

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00345

AC:

3775

AN:

1095492

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

1199

AN XY:

360956

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

26347

American (AMR)

AF:

0.000370

AC:

AN:

35178

Ashkenazi Jewish (ASJ)

AF:

0.00269

AC:

AN:

19358

East Asian (EAS)

AF:

0.00

AC:

AN:

30178

South Asian (SAS)

AF:

0.00

AC:

AN:

54001

European-Finnish (FIN)

AF:

0.000839

AC:

AN:

40518

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.00421

AC:

3532

AN:

839785

Other (OTH)

AF:

0.00285

AC:

131

AN:

45993

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

126

253

379

506

632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

264

396

528

660

<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:

0.00235

AC:

263

AN:

111928

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

AN XY:

34138

show subpopulations

African (AFR)

AF:

0.000713

AC:

AN:

30840

American (AMR)

AF:

0.000478

AC:

AN:

10459

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3593

South Asian (SAS)

AF:

0.00

AC:

AN:

2717

European-Finnish (FIN)

AF:

0.000498

AC:

AN:

6027

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00425

AC:

226

AN:

53226

Other (OTH)

AF:

0.000659

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

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:

0.00346

Hom.:

150

Bravo

AF:

0.00191

EpiCase

AF:

0.00327

EpiControl

AF:

0.00333

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Spermatogenic failure, X-linked, 2 (1)

TEX11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.6

(source)

DANN

Benign

0.80

PhyloP100

-0.29

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.018

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

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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