Variant chr11-78658357-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2

The NM_001098816.3(TENM4):c.8011G>A(p.Gly2671Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00092 in 1,613,868 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 8 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 9 hom. )

Consequence

TENM4
NM_001098816.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.71

Variant links:

Genes affected

TENM4 (HGNC:29945): (teneurin transmembrane protein 4) The protein encoded by this gene plays a role in establishing proper neuronal connectivity during development. Defects in this gene have been associated with hereditary essential tremor-5. [provided by RefSeq, Oct 2016]

TENM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TENM4. . Gene score misZ 2.7323 (greater than the threshold 3.09). Trascript score misZ 3.5261 (greater than threshold 3.09). GenCC has associacion of gene with tremor, hereditary essential, 5.

BP4

Computational evidence support a benign effect (MetaRNN=0.008531839).

BP6

Variant 11-78658357-C-T is Benign according to our data. Variant chr11-78658357-C-T is described in ClinVar as [Benign]. Clinvar id is 710060.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00466 (710/152336) while in subpopulation AFR AF= 0.016 (666/41566). AF 95% confidence interval is 0.015. There are 8 homozygotes in gnomad4. There are 312 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 710 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM4	NM_001098816.3 linkuse as main transcript	c.8011G>A	p.Gly2671Arg	missense_variant	34/34	ENST00000278550.12	NP_001092286.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TENM4	ENST00000278550.12 linkuse as main transcript	c.8011G>A	p.Gly2671Arg	missense_variant	34/34	5	NM_001098816.3	ENSP00000278550	P1
TENM4	ENST00000530738.1 linkuse as main transcript	c.2801-303G>A		intron_variant		2		ENSP00000431711

Frequencies

GnomAD3 genomes

AF:

0.00464

AC:

707

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.000176

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00124

AC:

309

AN:

248698

Hom.:

AF XY:

0.000978

AC XY:

132

AN XY:

134940

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.000958

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.000530

AC:

775

AN:

1461532

Hom.:

Cov.:

AF XY:

0.000442

AC XY:

321

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.000663

GnomAD4 genome

AF:

0.00466

AC:

710

AN:

152336

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

312

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0160

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.000986

Hom.:

Bravo

AF:

0.00544

ESP6500AA

AF:

0.0160

AC:

ESP6500EA

AF:

0.000118

AC:

ExAC

AF:

0.00145

AC:

176

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

TENM4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

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). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0085

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.53

Sift

Benign

0.076

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.25

MutPred

0.64

Gain of MoRF binding (P = 0.0075);

MVP

0.33

MPC

0.35

ClinPred

0.084

GERP RS

4.4

Varity_R

0.42

gMVP

0.73

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