X-70554698-A-G

Position:

• chrX-70554698-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_031276.3(TEX11):​c.2243T>C​(p.Val748Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000257 in 1,207,826 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 105 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00017 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00027 (0 hom. 100 hem.)
• Consequence: TEX11 NM_031276.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.46

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.043995053).
• BP6: Variant X-70554698-A-G is Benign according to our data. Variant chrX-70554698-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 981147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Hemizygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3	c.2243T>C	p.Val748Ala	missense_variant	26/30	ENST00000374333.7	NP_112566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX11	ENST00000374333.7	c.2243T>C	p.Val748Ala	missense_variant	26/30	1	NM_031276.3	ENSP00000363453	P2
TEX11	ENST00000344304.3	c.2288T>C	p.Val763Ala	missense_variant	25/29	5		ENSP00000340995	A2
TEX11	ENST00000395889.6	c.2288T>C	p.Val763Ala	missense_variant	27/31	2		ENSP00000379226	A2
TEX11	ENST00000374320.6	c.1313T>C	p.Val438Ala	missense_variant	15/19	2		ENSP00000363440

Frequencies

GnomAD3 genomes AF: 0.000170 AC: 19 AN: 111847 Hom.: 0 Cov.: 23 AF XY: 0.000147 AC XY: 5 AN XY: 33995

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000951

Gnomad ASJ AF: 0.000756

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000329

Gnomad MID AF: 0.00837

Gnomad NFE AF: 0.000169

Gnomad OTH AF: 0.00133

GnomAD3 exomes AF: 0.000257 AC: 46 AN: 178986 Hom.: 0 AF XY: 0.000173 AC XY: 11 AN XY: 63722

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000189

Gnomad ASJ exome AF: 0.00217

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000166

Gnomad FIN exome AF: 0.000125

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.000683

GnomAD4 exome AF: 0.000266 AC: 291 AN: 1095926 Hom.: 0 Cov.: 30 AF XY: 0.000277 AC XY: 100 AN XY: 361568

Gnomad4 AFR exome AF: 0.000190

Gnomad4 AMR exome AF: 0.000200

Gnomad4 ASJ exome AF: 0.00155

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000447

Gnomad4 FIN exome AF: 0.000272

Gnomad4 NFE exome AF: 0.000209

Gnomad4 OTH exome AF: 0.000522

GnomAD4 genome AF: 0.000170 AC: 19 AN: 111900 Hom.: 0 Cov.: 23 AF XY: 0.000147 AC XY: 5 AN XY: 34058

Gnomad4 AFR AF: 0.0000324

Gnomad4 AMR AF: 0.0000950

Gnomad4 ASJ AF: 0.000756

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000329

Gnomad4 NFE AF: 0.000170

Gnomad4 OTH AF: 0.00131

Alfa AF: 0.000320 Hom.: 7

Bravo AF: 0.000253

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.000198 AC: 24

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 05, 2020

- -

TEX11-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 04, 2024

This variant is classified as 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
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	.;.;T;T
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.43	T;T;T;.
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.044	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	.;.;M;M
MutationTaster	Benign	0.94	N;N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.3	N;D;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.013	D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D
Polyphen		0.0080	B;.;B;B
Vest4		0.60
MVP		0.30
MPC		0.93
ClinPred		0.071	T
GERP RS		2.0
Varity_R		0.14
gMVP		0.29

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: rs200139216; hg19: chrX-69774548;