Variant chr11-78658167-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate

The NM_001098816.3(TENM4):c.8201T>G(p.Val2734Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TENM4
NM_001098816.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

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 Uncertain_significance. Variant got 3 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.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TENM4	NM_001098816.3 linkuse as main transcript	c.8201T>G	p.Val2734Gly	missense_variant	34/34	ENST00000278550.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TENM4	ENST00000278550.12 linkuse as main transcript	c.8201T>G	p.Val2734Gly	missense_variant	34/34	5	NM_001098816.3	P1
TENM4	ENST00000530738.1 linkuse as main transcript	c.2801-113T>G		intron_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00104

AC:

1509

AN:

1456010

Hom.:

Cov.:

AF XY:

0.000958

AC XY:

694

AN XY:

724498

show subpopulations

Gnomad4 AFR exome

AF:

0.000599

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000422

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00125

Gnomad4 OTH exome

AF:

0.000897

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.8201T>G (p.V2734G) alteration is located in exon 34 (coding exon 30) of the TENM4 gene. This alteration results from a T to G substitution at nucleotide position 8201, causing the valine (V) at amino acid position 2734 to be replaced by a glycine (G). 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

Pathogenic

0.63

BayesDel_addAF

Pathogenic

0.50

BayesDel_noAF

Pathogenic

0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Pathogenic

0.37

MetaRNN

Pathogenic

0.91

MetaSVM

Pathogenic

0.91

MutationAssessor

Pathogenic

3.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.7

REVEL

Pathogenic

0.94

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.73

MutPred

0.67

Gain of disorder (P = 0.016);

MVP

0.93

MPC

1.1

ClinPred

1.0

GERP RS

5.7

Varity_R

0.89

gMVP

0.88

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