Genetic Variant TENM3:c.233-63_233-62delAA (chr4-182346575-TAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001080477.4(TENM3):c.233-63_233-62delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 828,246 control chromosomes in the GnomAD database, including 490 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.044 ( 135 hom., cov: 0)

Exomes 𝑓: 0.15 ( 355 hom. )

Consequence

TENM3
NM_001080477.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

TENM3 (HGNC:29944): (teneurin transmembrane protein 3) This gene encodes a member of the teneurin transmembrane protein family. The encoded protein may be involved in the regulation of neuronal development including development of the visual pathway. Mutations in this gene have been associated with microphthalmia and developmental dysplasia of the hip. [provided by RefSeq, Jan 2023]

TENM3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 4-182346575-TAA-T is Benign according to our data. Variant chr4-182346575-TAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1326030.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4 link	c.233-63_233-62delAA		intron_variant	Intron 2 of 27	ENST00000511685.6	NP_001073946.1	Q9P273A0A140VJW8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TENM3	ENST00000511685.6 link	c.233-75_233-74delAA	intron_variant	Intron 2 of 27	5	NM_001080477.4	ENSP00000424226.1	Q9P273
TENM3	ENST00000513201.1 link	n.483-75_483-74delAA	intron_variant	Intron 2 of 3	1
TENM3	ENST00000512480.5 link	c.233-75_233-74delAA	intron_variant	Intron 2 of 2	3		ENSP00000421320.1	D6RGC5

Frequencies

GnomAD3 genomes

AF:

0.0439

AC:

6424

AN:

146178

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0376

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.0640

Gnomad ASJ

AF:

0.0459

Gnomad EAS

AF:

0.0365

Gnomad SAS

AF:

0.0519

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.0455

Gnomad NFE

AF:

0.0449

Gnomad OTH

AF:

0.0512

GnomAD4 exome

AF:

0.146

AC:

99308

AN:

682010

Hom.:

355

AF XY:

0.146

AC XY:

49795

AN XY:

340190

show subpopulations

Gnomad4 AFR exome

AF:

0.103

AC:

1767

AN:

17220

Gnomad4 AMR exome

AF:

0.186

AC:

2804

AN:

15070

Gnomad4 ASJ exome

AF:

0.115

AC:

1460

AN:

12732

Gnomad4 EAS exome

AF:

0.141

AC:

3333

AN:

23652

Gnomad4 SAS exome

AF:

0.157

AC:

6254

AN:

39768

Gnomad4 FIN exome

AF:

0.124

AC:

3481

AN:

27996

Gnomad4 NFE exome

AF:

0.148

AC:

75732

AN:

512256

Gnomad4 Remaining exome

AF:

0.137

AC:

4148

AN:

30310

Heterozygous variant carriers

5979

11959

17938

23918

29897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

2720

5440

8160

10880

13600

<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:

0.0440

AC:

6437

AN:

146236

Hom.:

135

Cov.:

AF XY:

0.0441

AC XY:

3129

AN XY:

70968

show subpopulations

Gnomad4 AFR

AF:

0.0378

AC:

0.0377996

AN:

0.0377996

Gnomad4 AMR

AF:

0.0639

AC:

0.0639424

AN:

0.0639424

Gnomad4 ASJ

AF:

0.0459

AC:

0.0459333

AN:

0.0459333

Gnomad4 EAS

AF:

0.0366

AC:

0.0366293

AN:

0.0366293

Gnomad4 SAS

AF:

0.0521

AC:

0.0521419

AN:

0.0521419

Gnomad4 FIN

AF:

0.0338

AC:

0.0337929

AN:

0.0337929

Gnomad4 NFE

AF:

0.0450

AC:

0.0449648

AN:

0.0449648

Gnomad4 OTH

AF:

0.0512

AC:

0.0512438

AN:

0.0512438

Heterozygous variant carriers

293

586

880

1173

1466

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0336

Hom.:

1991

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 16, 2021

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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