X-70610514-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_031276.3(TEX11):c.1781G>A(p.Cys594Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000531 in 1,205,491 control chromosomes in the GnomAD database, including 1 homozygotes. There are 20 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 0.000081 (0 hom., 3 hem., cov: 22)
  • Exomes 𝑓: 0.000050 (1 hom. 17 hem.)
• Consequence: TEX11 NM_031276.3 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.0800

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 (MetaRNN=0.014674038).
• BP6: Variant X-70610514-C-T is Benign according to our data. Variant chrX-70610514-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2660830.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
• BS2: High Hemizygotes in GnomAd at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX11	NM_031276.3	c.1781G>A	p.Cys594Tyr	missense_variant	21/30	ENST00000374333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX11	ENST00000374333.7	c.1781G>A	p.Cys594Tyr	missense_variant	21/30	1	NM_031276.3	P2
TEX11	ENST00000344304.3	c.1826G>A	p.Cys609Tyr	missense_variant	20/29	5		A2
TEX11	ENST00000395889.6	c.1826G>A	p.Cys609Tyr	missense_variant	22/31	2		A2
TEX11	ENST00000374320.6	c.851G>A	p.Cys284Tyr	missense_variant	10/19	2

Frequencies

GnomAD3 genomes AF: 0.0000810 AC: 9 AN: 111151 Hom.: 0 Cov.: 22 AF XY: 0.0000898 AC XY: 3 AN XY: 33391

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000958

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00225

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: 0.000223 AC: 40 AN: 179215 Hom.: 1 AF XY: 0.000188 AC XY: 12 AN XY: 63927

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00295

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000503 AC: 55 AN: 1094292 Hom.: 1 Cov.: 27 AF XY: 0.0000472 AC XY: 17 AN XY: 359946

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00183

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000809 AC: 9 AN: 111199 Hom.: 0 Cov.: 22 AF XY: 0.0000897 AC XY: 3 AN XY: 33449

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000957

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00226

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000106

ExAC AF: 0.000165 AC: 20

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.1826G>A (p.C609Y) alteration is located in exon 22 (coding exon 20) of the TEX11 gene. This alteration results from a G to A substitution at nucleotide position 1826, causing the cysteine (C) at amino acid position 609 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

TEX11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.1
Dann	Benign	0.20
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.63	T;T;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.015	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.58	N;N;N;N
REVEL	Benign	0.040
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.17
MutPred		0.43		.;.;Loss of catalytic residue at L610 (P = 0.0473);Loss of catalytic residue at L610 (P = 0.0473);
MVP		0.068
MPC		0.52
ClinPred		0.0078	T
GERP RS		0.76
Varity_R		0.064
gMVP		0.32

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: rs200375710; hg19: chrX-69830364;