rs143246552

Positions:

• chrX-70853093-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_031276.3(TEX11):​c.466A>G​(p.Met156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,207,138 control chromosomes in the GnomAD database, including 1 homozygotes. There are 111 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., 13 hem., cov: 22)
  • Exomes 𝑓: 0.00029 (1 hom. 98 hem.)
• Consequence: TEX11 NM_031276.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1 U:1 B:2
• Conservation: PhyloP100: -0.243

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007108569).
• BS2: High Hemizygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3	c.466A>G	p.Met156Val	missense_variant	7/30	ENST00000374333.7	NP_112566.2
TEX11	NM_001003811.2	c.511A>G	p.Met171Val	missense_variant	8/31		NP_001003811.1
TEX11	XM_017029649.1	c.466A>G	p.Met156Val	missense_variant	7/31		XP_016885138.1
TEX11	XM_011530994.2	c.466A>G	p.Met156Val	missense_variant	7/31		XP_011529296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX11	ENST00000374333.7	c.466A>G	p.Met156Val	missense_variant	7/30	1	NM_031276.3	ENSP00000363453.2
TEX11	ENST00000344304.3	c.511A>G	p.Met171Val	missense_variant	6/29	5		ENSP00000340995.3
TEX11	ENST00000395889.6	c.511A>G	p.Met171Val	missense_variant	8/31	2		ENSP00000379226.2

Frequencies

GnomAD3 genomes AF: 0.000495 AC: 55 AN: 111201 Hom.: 0 Cov.: 22 AF XY: 0.000389 AC XY: 13 AN XY: 33385

Gnomad AFR AF: 0.00163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000967

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00113

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000440 AC: 79 AN: 179693 Hom.: 0 AF XY: 0.000327 AC XY: 21 AN XY: 64311

Gnomad AFR exome AF: 0.00169

Gnomad AMR exome AF: 0.000331

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00336

Gnomad SAS exome AF: 0.0000548

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000225

GnomAD4 exome AF: 0.000287 AC: 315 AN: 1095879 Hom.: 1 Cov.: 30 AF XY: 0.000271 AC XY: 98 AN XY: 361335

Gnomad4 AFR exome AF: 0.00201

Gnomad4 AMR exome AF: 0.000342

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00799

Gnomad4 SAS exome AF: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.000174

GnomAD4 genome AF: 0.000494 AC: 55 AN: 111259 Hom.: 0 Cov.: 22 AF XY: 0.000389 AC XY: 13 AN XY: 33453

Gnomad4 AFR AF: 0.00163

Gnomad4 AMR AF: 0.0000966

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00113

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000280 Hom.: 9

Bravo AF: 0.000718

ESP6500AA AF: 0.00183 AC: 7

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000437 AC: 53

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1 Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1 Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2024	The p.Met171Val variant in TEX11 is classified as likely benign because it has been identified in 0.73% (245/33686) of East Asian chromosomes including 82 hemizygotes and 1 homozygote by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4. -
Uncertain significance, criteria provided, single submitter	clinical testing	Mendelics	May 04, 2022	- -

Spermatogenic failure, X-linked, 2 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 28, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.95	T
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.0020
DANN	Benign	0.31
DEOGEN2	Benign	0.035	.;T;T
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.28	T;T;.
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.0071	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.83	.;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.010	N;N;N
REVEL	Benign	0.0080
Sift	Benign	0.57	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.025
MVP		0.043
MPC		0.31
ClinPred		0.0066	T
GERP RS		-5.8
Varity_R		0.046
gMVP		0.085

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

LitVar

Other links and lift over

dbSNP: rs143246552; hg19: chrX-70072943;