X-70552198-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031276.3(TEX11):c.2448G>A(p.Ser816=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,209,352 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 74 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 0.00016 (0 hom., 6 hem., cov: 22)
  • Exomes 𝑓: 0.00017 (0 hom. 68 hem.)
• Consequence: TEX11 NM_031276.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.12

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant X-70552198-C-T is Benign according to our data. Variant chrX-70552198-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3047439.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.12 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX11	NM_031276.3	c.2448G>A	p.Ser816=	synonymous_variant	28/30	ENST00000374333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX11	ENST00000374333.7	c.2448G>A	p.Ser816=	synonymous_variant	28/30	1	NM_031276.3	P2
TEX11	ENST00000344304.3	c.2493G>A	p.Ser831=	synonymous_variant	27/29	5		A2
TEX11	ENST00000395889.6	c.2493G>A	p.Ser831=	synonymous_variant	29/31	2		A2
TEX11	ENST00000374320.6	c.1518G>A	p.Ser506=	synonymous_variant	17/19	2

Frequencies

GnomAD3 genomes AF: 0.000161 AC: 18 AN: 111862 Hom.: 0 Cov.: 22 AF XY: 0.000176 AC XY: 6 AN XY: 34044

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000319

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000137 AC: 25 AN: 182316 Hom.: 0 AF XY: 0.000180 AC XY: 12 AN XY: 66812

Gnomad AFR exome AF: 0.0000763

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.000222

GnomAD4 exome AF: 0.000169 AC: 186 AN: 1097490 Hom.: 0 Cov.: 30 AF XY: 0.000187 AC XY: 68 AN XY: 362896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

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: 0.000213

Gnomad4 OTH exome AF: 0.000130

GnomAD4 genome AF: 0.000161 AC: 18 AN: 111862 Hom.: 0 Cov.: 22 AF XY: 0.000176 AC XY: 6 AN XY: 34044

Gnomad4 AFR AF: 0.0000325

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000319

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000185

EpiCase AF: 0.0000549

EpiControl AF: 0.000239

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

TEX11-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 06, 2019

This variant is classified as likely 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
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.18
Dann	Benign	0.39

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: rs144951375; hg19: chrX-69772048; COSMIC: COSV105232504;