X-70552150-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_031276.3(TEX11):c.2496T>G(p.Asp832Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 1,209,155 control chromosomes in the GnomAD database, including 8 homozygotes. There are 238 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. D832D) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., 13 hem., cov: 22)
  • Exomes 𝑓: 0.00066 (8 hom. 225 hem.)
• Consequence: TEX11 NM_031276.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055111945).
• BP6: Variant X-70552150-A-C is Benign according to our data. Variant chrX-70552150-A-C is described in ClinVar as [Benign]. Clinvar id is 789463.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.000657 (721/1097254) while in subpopulation EAS AF= 0.022 (664/30173). AF 95% confidence interval is 0.0206. There are 8 homozygotes in gnomad4_exome. There are 225 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX11	NM_031276.3	c.2496T>G	p.Asp832Glu	missense_variant	28/30	ENST00000374333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX11	ENST00000374333.7	c.2496T>G	p.Asp832Glu	missense_variant	28/30	1	NM_031276.3	P2
TEX11	ENST00000344304.3	c.2541T>G	p.Asp847Glu	missense_variant	27/29	5		A2
TEX11	ENST00000395889.6	c.2541T>G	p.Asp847Glu	missense_variant	29/31	2		A2
TEX11	ENST00000374320.6	c.1566T>G	p.Asp522Glu	missense_variant	17/19	2

Frequencies

GnomAD3 genomes AF: 0.000393 AC: 44 AN: 111847 Hom.: 0 Cov.: 22 AF XY: 0.000382 AC XY: 13 AN XY: 34027

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0112

Gnomad SAS AF: 0.000377

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000956 AC: 173 AN: 181021 Hom.: 0 AF XY: 0.000869 AC XY: 57 AN XY: 65593

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000745

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0105

Gnomad SAS exome AF: 0.000489

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000657 AC: 721 AN: 1097254 Hom.: 8 Cov.: 30 AF XY: 0.000620 AC XY: 225 AN XY: 362674

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000600

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0220

Gnomad4 SAS exome AF: 0.000315

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.00000832

Gnomad4 OTH exome AF: 0.000239

GnomAD4 genome AF: 0.000393 AC: 44 AN: 111901 Hom.: 0 Cov.: 22 AF XY: 0.000381 AC XY: 13 AN XY: 34091

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0112

Gnomad4 SAS AF: 0.000378

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000188

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000113 Hom.: 1289

ExAC AF: 0.000914 AC: 111

EpiCase AF: 0.00

EpiControl AF: 0.0000597

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	14
Dann	Benign	0.50
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.71	T;T;T;.
MetaRNN	Benign	0.0055	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.40	N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.83	T;T;T;T
Sift4G	Benign	0.85	T;T;T;T
Polyphen		0.88	P;.;P;P
Vest4		0.053
MutPred		0.29		.;.;Gain of solvent accessibility (P = 0.1751);Gain of solvent accessibility (P = 0.1751);
MVP		0.41
MPC		0.59
ClinPred		0.065	T
GERP RS		2.5
Varity_R		0.066
gMVP		0.070

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: rs16991177; hg19: chrX-69772000;