Variant 11-78658253-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001098816.3(TENM4):c.8115C>T(p.Arg2705=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,613,628 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 15 hom. )

Consequence

TENM4
NM_001098816.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.80

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 11-78658253-G-A is Benign according to our data. Variant chr11-78658253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642203.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00117 (1710/1461282) while in subpopulation EAS AF= 0.0186 (739/39686). AF 95% confidence interval is 0.0175. There are 15 homozygotes in gnomad4_exome. There are 856 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 207 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TENM4	NM_001098816.3 linkuse as main transcript	c.8115C>T	p.Arg2705=	synonymous_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.8115C>T	p.Arg2705=	synonymous_variant	34/34	5	NM_001098816.3	ENSP00000278550	P1
TENM4	ENST00000530738.1 linkuse as main transcript	c.2801-199C>T		intron_variant		2		ENSP00000431711

Frequencies

GnomAD3 genomes

AF:

0.00136

AC:

207

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00924

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00180

AC:

447

AN:

248274

Hom.:

AF XY:

0.00175

AC XY:

236

AN XY:

134786

show subpopulations

Gnomad AFR exome

AF:

0.000777

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00768

Gnomad EAS exome

AF:

0.00825

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.00689

Gnomad NFE exome

AF:

0.000365

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.00117

AC:

1710

AN:

1461282

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

856

AN XY:

726878

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00774

Gnomad4 EAS exome

AF:

0.0186

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.00700

Gnomad4 NFE exome

AF:

0.000232

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00136

AC:

207

AN:

152346

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

130

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00926

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00810

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000907

Hom.:

Bravo

AF:

0.000771

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

TENM4: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.16

DANN

Benign

0.57

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

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