NM_001080477.4:c.2083dupA
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001080477.4(TENM3):c.2083dupA(p.Thr695AsnfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,576 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TENM3
NM_001080477.4 frameshift
NM_001080477.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.541
Publications
6 publications found
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 9Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
- microphthalmia, isolated, with colobomaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 4-182688212-G-GA is Pathogenic according to our data. Variant chr4-182688212-G-GA is described in ClinVar as Pathogenic. ClinVar VariationId is 41420.Status of the report is no_assertion_criteria_provided, 0 stars.
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
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TENM3 | NM_001080477.4 | MANE Select | c.2083dupA | p.Thr695AsnfsTer5 | frameshift | Exon 12 of 28 | NP_001073946.1 | Q9P273 | |
| TENM3 | NM_001415969.1 | c.2083dupA | p.Thr695AsnfsTer5 | frameshift | Exon 12 of 29 | NP_001402898.1 | |||
| TENM3 | NM_001415970.1 | c.2083dupA | p.Thr695AsnfsTer5 | frameshift | Exon 12 of 29 | NP_001402899.1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TENM3 | ENST00000511685.6 | TSL:5 MANE Select | c.2083dupA | p.Thr695AsnfsTer5 | frameshift | Exon 12 of 28 | ENSP00000424226.1 | Q9P273 | |
| TENM3 | ENST00000851056.1 | c.2083dupA | p.Thr695AsnfsTer5 | frameshift | Exon 12 of 31 | ENSP00000521125.1 | |||
| TENM3 | ENST00000851057.1 | c.2083dupA | p.Thr695AsnfsTer5 | frameshift | Exon 12 of 31 | ENSP00000521126.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461576Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727064 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1461576
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
727064
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33472
American (AMR)
AF:
AC:
0
AN:
44706
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86222
European-Finnish (FIN)
AF:
AC:
0
AN:
53398
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111806
Other (OTH)
AF:
AC:
0
AN:
60370
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Microphthalmia, isolated, with coloboma 9 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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