Variant ENST00000371130.7:c.6849G>A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The ENST00000371130.7(TENM1):c.6849G>A(p.Leu2283Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00036 in 1,209,764 control chromosomes in the GnomAD database, including 2 homozygotes. There are 108 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., 60 hem., cov: 22)

Exomes 𝑓: 0.00018 ( 2 hom. 48 hem. )

Consequence

TENM1
ENST00000371130.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

TENM1 (HGNC:8117): (teneurin transmembrane protein 1) The protein encoded by this gene belongs to the tenascin family and teneurin subfamily. It is expressed in the neurons and may function as a cellular signal transducer. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

TENM1 links:

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

STAG2 links:

LOC105373331 (HGNC:):

LOC105373331 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant X-124384061-C-T is Benign according to our data. Variant chrX-124384061-C-T is described in ClinVar as [Benign]. Clinvar id is 3041444.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=2.52 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
TENM1	NM_001163278.2 link	c.6870G>A	p.Leu2290Leu	synonymous_variant	Exon 33 of 35	NP_001156750.1	Q9UKZ4-2
TENM1	NM_001163279.1 link	c.6867G>A	p.Leu2289Leu	synonymous_variant	Exon 30 of 32	NP_001156751.1	Q9UKZ4B7ZMH4
TENM1	NM_014253.3 link	c.6849G>A	p.Leu2283Leu	synonymous_variant	Exon 29 of 31	NP_055068.2	Q9UKZ4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
TENM1	ENST00000371130.7 link	c.6849G>A	p.Leu2283Leu	synonymous_variant	Exon 29 of 31	1	ENSP00000360171.3	Q9UKZ4-1
TENM1	ENST00000422452.3 link	c.6816G>A	p.Leu2272Leu	synonymous_variant	Exon 33 of 35	1	ENSP00000403954.4	A0A8Z5AZJ6
STAG2	ENST00000469481.1 link	n.454-27761C>T		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00209

AC:

234

AN:

111696

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

AN XY:

33872

show subpopulations

Gnomad AFR

AF:

0.00730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000473

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:

0.0000188

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.000553

AC:

101

AN:

182648

Hom.:

AF XY:

0.000445

AC XY:

AN XY:

67410

show subpopulations

Gnomad AFR exome

AF:

0.00730

Gnomad AMR exome

AF:

0.000146

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:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

201

AN:

1098017

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

363395

show subpopulations

Gnomad4 AFR exome

AF:

0.00614

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000356

Gnomad4 OTH exome

AF:

0.000651

GnomAD4 genome

AF:

0.00209

AC:

234

AN:

111747

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

AN XY:

33933

show subpopulations

Gnomad4 AFR

AF:

0.00729

Gnomad4 AMR

AF:

0.000472

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.000695

Hom.:

Bravo

AF:

0.00226

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TENM1-related disorder

Benign:1

Jan 28, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.4

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over