Genetic Variant NM_001395460.1:c.712+117G>A (chr5-167876312-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001395460.1(TENM2):c.712+117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.815 in 829,332 control chromosomes in the GnomAD database, including 280,952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 42613 hom., cov: 31)

Exomes 𝑓: 0.83 ( 238339 hom. )

Consequence

TENM2
NM_001395460.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.374

Publications

4 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395460.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TENM2	NM_001395460.1	MANE Select	c.712+117G>A	intron	N/A	NP_001382389.1
TENM2	NM_001122679.2		c.712+117G>A	intron	N/A	NP_001116151.1
TENM2	NM_001368145.1		c.256+117G>A	intron	N/A	NP_001355074.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TENM2	ENST00000518659.6	TSL:5 MANE Select	c.712+117G>A	intron	N/A	ENSP00000429430.1
TENM2	ENST00000520394.5	TSL:1	c.140-76276G>A	intron	N/A	ENSP00000427874.1
TENM2	ENST00000519204.5	TSL:5	c.349+117G>A	intron	N/A	ENSP00000428964.1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110157

AN:

151906

Hom.:

42590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.837

Gnomad AMR

AF:

0.797

Gnomad ASJ

AF:

0.787

Gnomad EAS

AF:

0.980

Gnomad SAS

AF:

0.895

Gnomad FIN

AF:

0.846

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.835

Gnomad OTH

AF:

0.733

GnomAD4 exome

AF:

0.835

AC:

565481

AN:

677308

Hom.:

238339

AF XY:

0.839

AC XY:

294953

AN XY:

351502

show subpopulations

African (AFR)

AF:

0.413

AC:

7304

AN:

17682

American (AMR)

AF:

0.844

AC:

26515

AN:

31424

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

13870

AN:

17712

East Asian (EAS)

AF:

0.987

AC:

31910

AN:

32316

South Asian (SAS)

AF:

0.904

AC:

51503

AN:

56952

European-Finnish (FIN)

AF:

0.854

AC:

29252

AN:

34242

Middle Eastern (MID)

AF:

0.820

AC:

3347

AN:

4082

European-Non Finnish (NFE)

AF:

0.834

AC:

374371

AN:

448786

Other (OTH)

AF:

0.803

AC:

27409

AN:

34112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4669

9338

14006

18675

23344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4930

9860

14790

19720

24650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.725

AC:

110215

AN:

152024

Hom.:

42613

Cov.:

AF XY:

0.732

AC XY:

54415

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.427

AC:

17687

AN:

41422

American (AMR)

AF:

0.797

AC:

12161

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.787

AC:

2730

AN:

3470

East Asian (EAS)

AF:

0.980

AC:

5066

AN:

5168

South Asian (SAS)

AF:

0.896

AC:

4316

AN:

4818

European-Finnish (FIN)

AF:

0.846

AC:

8959

AN:

10584

Middle Eastern (MID)

AF:

0.738

AC:

217

AN:

294

European-Non Finnish (NFE)

AF:

0.835

AC:

56762

AN:

67984

Other (OTH)

AF:

0.736

AC:

1555

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1287

2574

3860

5147

6434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.778

Hom.:

7505

Bravo

AF:

0.707

Asia WGS

AF:

0.867

AC:

3015

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.65

(source)

DANN

Benign

0.21

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over