NM_001080477.4:c.777T>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001080477.4(TENM3):c.777T>G(p.Gly259Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 1,596,730 control chromosomes in the GnomAD database, including 5,494 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 417 hom., cov: 31)

Exomes 𝑓: 0.079 ( 5077 hom. )

Consequence

TENM3
NM_001080477.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.10

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

microphthalmia, isolated, with coloboma 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
microphthalmia, isolated, with coloboma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TENM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 4-182628678-T-G is Benign according to our data. Variant chr4-182628678-T-G is described in ClinVar as Benign. ClinVar VariationId is 257356.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4 link	c.777T>G	p.Gly259Gly	synonymous_variant	Exon 5 of 28	ENST00000511685.6	NP_001073946.1	Q9P273A0A140VJW8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TENM3	ENST00000511685.6 link	c.777T>G	p.Gly259Gly	synonymous_variant	Exon 5 of 28	5	NM_001080477.4	ENSP00000424226.1		Q9P273
TENM3	ENST00000510504.1 link	c.351T>G	p.Gly117Gly	synonymous_variant	Exon 3 of 3	3		ENSP00000426914.1		H0YAF0

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9772

AN:

152102

Hom.:

417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.0597

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.0285

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0796

Gnomad OTH

AF:

0.0659

GnomAD2 exomes

AF:

0.0758

AC:

17172

AN:

226490

AF XY:

0.0790

show subpopulations

Gnomad AFR exome

AF:

0.0222

Gnomad AMR exome

AF:

0.0393

Gnomad ASJ exome

AF:

0.126

Gnomad EAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0366

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0880

GnomAD4 exome

AF:

0.0792

AC:

114439

AN:

1444510

Hom.:

5077

Cov.:

AF XY:

0.0805

AC XY:

57673

AN XY:

716812

show subpopulations

African (AFR)

AF:

0.0235

AC:

778

AN:

33146

American (AMR)

AF:

0.0416

AC:

1770

AN:

42534

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

3149

AN:

25732

East Asian (EAS)

AF:

0.142

AC:

5546

AN:

39106

South Asian (SAS)

AF:

0.113

AC:

9403

AN:

83224

European-Finnish (FIN)

AF:

0.0369

AC:

1944

AN:

52618

Middle Eastern (MID)

AF:

0.0818

AC:

470

AN:

5746

European-Non Finnish (NFE)

AF:

0.0783

AC:

86320

AN:

1102560

Other (OTH)

AF:

0.0845

AC:

5059

AN:

59844

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4885

9771

14656

19542

24427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3302

6604

9906

13208

16510

<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:

0.0642

AC:

9778

AN:

152220

Hom.:

417

Cov.:

AF XY:

0.0629

AC XY:

4682

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0254

AC:

1057

AN:

41542

American (AMR)

AF:

0.0595

AC:

910

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

396

AN:

3470

East Asian (EAS)

AF:

0.143

AC:

740

AN:

5164

South Asian (SAS)

AF:

0.119

AC:

572

AN:

4816

European-Finnish (FIN)

AF:

0.0285

AC:

303

AN:

10614

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0796

AC:

5415

AN:

68004

Other (OTH)

AF:

0.0666

AC:

141

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

446

893

1339

1786

2232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

122

244

366

488

610

<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:

0.0759

Hom.:

253

Bravo

AF:

0.0646

Asia WGS

AF:

0.113

AC:

392

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

-0.48

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

3.1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over