X-70553406-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031276.3(TEX11):c.2299A>G(p.Met767Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,070,396 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M767T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.3e-7 (0 hom. 0 hem.)
• Consequence: TEX11 NM_031276.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.82

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21173006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX11	NM_031276.3	c.2299A>G	p.Met767Val	missense_variant	27/30	ENST00000374333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX11	ENST00000374333.7	c.2299A>G	p.Met767Val	missense_variant	27/30	1	NM_031276.3	P2
TEX11	ENST00000344304.3	c.2344A>G	p.Met782Val	missense_variant	26/29	5		A2
TEX11	ENST00000395889.6	c.2344A>G	p.Met782Val	missense_variant	28/31	2		A2
TEX11	ENST00000374320.6	c.1369A>G	p.Met457Val	missense_variant	16/19	2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.34e-7 AC: 1 AN: 1070396 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 338032

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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 Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.2344A>G (p.M782V) alteration is located in exon 28 (coding exon 26) of the TEX11 gene. This alteration results from a A to G substitution at nucleotide position 2344, causing the methionine (M) at amino acid position 782 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
Cadd	Benign	3.3
Dann	Benign	0.77
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.71	T;T;T;.
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.98	N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-2.3	N;D;N;N
REVEL	Benign	0.074
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.081	T;T;T;T
Polyphen		0.021	B;.;B;B
Vest4		0.16
MutPred		0.71		.;.;Gain of ubiquitination at K784 (P = 0.0954);Gain of ubiquitination at K784 (P = 0.0954);
MVP		0.082
MPC		0.31
ClinPred		0.14	T
GERP RS		1.1
Varity_R		0.13
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69773256;