Genetic Variant TENM3:c.233-13dupT (chr4-182346631-C-CT) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS1

The NM_001080477.4(TENM3):c.233-13dupT variant causes a intron change. The variant allele was found at a frequency of 0.000437 in 1,603,410 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00024 ( 1 hom. )

Consequence

TENM3
NM_001080477.4 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.93

Publications

0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
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: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 4-182346631-C-CT is Benign according to our data. Variant chr4-182346631-C-CT is described in ClinVar as Benign. ClinVar VariationId is 1899079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00228 (346/151464) while in subpopulation AFR AF = 0.00803 (332/41340). AF 95% confidence interval is 0.00732. There are 1 homozygotes in GnomAd4. There are 157 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080477.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TENM3	NM_001080477.4	MANE Select	c.233-13dupT	intron	N/A	NP_001073946.1	Q9P273
TENM3	NM_001415969.1		c.233-13dupT	intron	N/A	NP_001402898.1
TENM3	NM_001415970.1		c.233-13dupT	intron	N/A	NP_001402899.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TENM3	ENST00000511685.6	TSL:5 MANE Select	c.233-20_233-19insT	intron	N/A	ENSP00000424226.1	Q9P273
TENM3	ENST00000513201.1	TSL:1	n.483-20_483-19insT	intron	N/A
TENM3	ENST00000851056.1		c.233-20_233-19insT	intron	N/A	ENSP00000521125.1

Frequencies

GnomAD3 genomes

AF:

0.00229

AC:

347

AN:

151368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00808

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.000962

GnomAD2 exomes

AF:

0.000570

AC:

138

AN:

242210

AF XY:

0.000403

show subpopulations

Gnomad AFR exome

AF:

0.00836

Gnomad AMR exome

AF:

0.000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000244

AC:

355

AN:

1451946

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

132

AN XY:

722422

show subpopulations

African (AFR)

AF:

0.00931

AC:

309

AN:

33200

American (AMR)

AF:

0.000226

AC:

AN:

44312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25820

East Asian (EAS)

AF:

0.00

AC:

AN:

39590

South Asian (SAS)

AF:

0.0000234

AC:

AN:

85634

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53238

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.00000543

AC:

AN:

1104474

Other (OTH)

AF:

0.000450

AC:

AN:

59996

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00228

AC:

346

AN:

151464

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

157

AN XY:

74004

show subpopulations

African (AFR)

AF:

0.00803

AC:

332

AN:

41340

American (AMR)

AF:

0.000657

AC:

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67854

Other (OTH)

AF:

0.000952

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000481

Hom.:

Bravo

AF:

0.00257

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.9

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

4-182346631-CT-CTT

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