rs147088100

Positions:

• chrX-70853248-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_031276.3(TEX11):​c.405C>T​(p.Ala135=) 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:1 B:3
• Conservation: PhyloP100: -0.286

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.286 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3	c.405C>T	p.Ala135=	splice_region_variant, synonymous_variant	6/30	ENST00000374333.7	NP_112566.2
TEX11	NM_001003811.2	c.450C>T	p.Ala150=	splice_region_variant, synonymous_variant	7/31		NP_001003811.1
TEX11	XM_017029649.1	c.405C>T	p.Ala135=	splice_region_variant, synonymous_variant	6/31		XP_016885138.1
TEX11	XM_011530994.2	c.405C>T	p.Ala135=	splice_region_variant, synonymous_variant	6/31		XP_011529296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX11	ENST00000374333.7	c.405C>T	p.Ala135=	splice_region_variant, synonymous_variant	6/30	1	NM_031276.3	ENSP00000363453	P2
TEX11	ENST00000344304.3	c.450C>T	p.Ala150=	splice_region_variant, synonymous_variant	5/29	5		ENSP00000340995	A2
TEX11	ENST00000395889.6	c.450C>T	p.Ala150=	splice_region_variant, synonymous_variant	7/31	2		ENSP00000379226	A2

Frequencies

GnomAD3 genomes AF: 0.00235 AC: 263 AN: 111875 Hom.: 2 Cov.: 23 AF XY: 0.00226 AC XY: 77 AN XY: 34075

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

GnomAD3 exomes AF: 0.00192 AC: 351 AN: 182786 Hom.: 1 AF XY: 0.00172 AC XY: 116 AN XY: 67304

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 SAS 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.: 4 Cov.: 29 AF XY: 0.00332 AC XY: 1199 AN XY: 360956

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.000370

Gnomad4 ASJ exome AF: 0.00269

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000839

Gnomad4 NFE exome AF: 0.00421

Gnomad4 OTH exome AF: 0.00285

GnomAD4 genome AF: 0.00235 AC: 263 AN: 111928 Hom.: 2 Cov.: 23 AF XY: 0.00226 AC XY: 77 AN XY: 34138

Gnomad4 AFR AF: 0.000713

Gnomad4 AMR AF: 0.000478

Gnomad4 ASJ AF: 0.00226

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000498

Gnomad4 NFE AF: 0.00425

Gnomad4 OTH AF: 0.000659

Alfa AF: 0.00365 Hom.: 147

Bravo AF: 0.00191

EpiCase AF: 0.00327

EpiControl AF: 0.00333

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	TEX11: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Spermatogenic failure, X-linked, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 28, 2015

- -

TEX11-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 25, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.6
DANN	Benign	0.80

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

LitVar

Other links and lift over

dbSNP: rs147088100; hg19: chrX-70073098;