Genetic Variant NM_001395460.1:c.6009C>T (chr5-168246948-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

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

The NM_001395460.1(TENM2):c.6009C>T(p.Asp2003Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,613,932 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 42 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 29 hom. )

Consequence

TENM2
NM_001395460.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.814

Variant links:

Genes affected

TENM2 (HGNC:29943): (teneurin transmembrane protein 2) Enables cell adhesion molecule binding activity and signaling receptor binding activity. Involved in several processes, including calcium-mediated signaling using intracellular calcium source; heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; and retrograde trans-synaptic signaling by trans-synaptic protein complex. Located in cell-cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TENM2 links:

TENM2-AS1 (HGNC:56066): (TENM2 antisense RNA 2)

TENM2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 5-168246948-C-T is Benign according to our data. Variant chr5-168246948-C-T is described in ClinVar as [Benign]. Clinvar id is 780964.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.814 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0121 (1840/152232) while in subpopulation AFR AF= 0.0408 (1694/41524). AF 95% confidence interval is 0.0392. There are 42 homozygotes in gnomad4. There are 884 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1840 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM2	NM_001395460.1 link	c.6009C>T	p.Asp2003Asp	synonymous_variant	Exon 29 of 31	ENST00000518659.6	NP_001382389.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM2	ENST00000518659.6 link	c.6009C>T	p.Asp2003Asp	synonymous_variant	Exon 29 of 31	5	NM_001395460.1	ENSP00000429430.1		Q9NT68-1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1831

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00310

AC:

773

AN:

249258

Hom.:

AF XY:

0.00224

AC XY:

303

AN XY:

135220

show subpopulations

Gnomad AFR exome

AF:

0.0423

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00149

GnomAD4 exome

AF:

0.00129

AC:

1892

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

787

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0413

Gnomad4 AMR exome

AF:

0.00230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000162

Gnomad4 OTH exome

AF:

0.00346

GnomAD4 genome

AF:

0.0121

AC:

1840

AN:

152232

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

884

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.00648

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0119

Alfa

AF:

0.00585

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 27, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.8

DANN

Benign

0.74

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