NM_001080477.4:c.3579T>C

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.3579T>C(p.Tyr1193Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,556 control chromosomes in the GnomAD database, including 69,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6832 hom., cov: 33)

Exomes 𝑓: 0.29 ( 62285 hom. )

Consequence

TENM3
NM_001080477.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.552

Publications

15 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=-0.68).

BP6

Variant 4-182743369-T-C is Benign according to our data. Variant chr4-182743369-T-C is described in ClinVar as Benign. ClinVar VariationId is 257350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.552 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TENM3	NM_001080477.4 link	c.3579T>C	p.Tyr1193Tyr	synonymous_variant	Exon 19 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.3579T>C	p.Tyr1193Tyr	synonymous_variant	Exon 19 of 28	5	NM_001080477.4	ENSP00000424226.1		Q9P273
TENM3	ENST00000502950.1 link	n.1966T>C		non_coding_transcript_exon_variant	Exon 11 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44557

AN:

151996

Hom.:

6830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.270

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.173

Gnomad FIN

AF:

0.322

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.282

GnomAD2 exomes

AF:

0.257

AC:

63948

AN:

249150

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.346

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.304

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.286

AC:

418634

AN:

1461442

Hom.:

62285

Cov.:

AF XY:

0.283

AC XY:

205808

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.344

AC:

11506

AN:

33476

American (AMR)

AF:

0.142

AC:

6342

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

6715

AN:

26136

East Asian (EAS)

AF:

0.144

AC:

5710

AN:

39698

South Asian (SAS)

AF:

0.180

AC:

15562

AN:

86250

European-Finnish (FIN)

AF:

0.326

AC:

17432

AN:

53398

Middle Eastern (MID)

AF:

0.208

AC:

1198

AN:

5766

European-Non Finnish (NFE)

AF:

0.304

AC:

337535

AN:

1111638

Other (OTH)

AF:

0.276

AC:

16634

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

15814

31629

47443

63258

79072

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10904

21808

32712

43616

54520

<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:

0.293

AC:

44587

AN:

152114

Hom.:

6832

Cov.:

AF XY:

0.288

AC XY:

21415

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.347

AC:

14394

AN:

41498

American (AMR)

AF:

0.184

AC:

2819

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

937

AN:

3464

East Asian (EAS)

AF:

0.153

AC:

790

AN:

5158

South Asian (SAS)

AF:

0.173

AC:

833

AN:

4824

European-Finnish (FIN)

AF:

0.322

AC:

3407

AN:

10576

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.304

AC:

20639

AN:

67986

Other (OTH)

AF:

0.282

AC:

596

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1642

3283

4925

6566

8208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.296

Hom.:

20633

Bravo

AF:

0.288

Asia WGS

AF:

0.205

AC:

714

AN:

3478

EpiCase

AF:

0.286

EpiControl

AF:

0.286

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 08, 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. -

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

-0.68

CADD

Benign

0.46

(source)

DANN

Benign

0.23

PhyloP100

-0.55

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