NM_152448.3:c.544dupA
Variant names:
Variant summary
Our verdict is Likely pathogenic. The variant received 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_152448.3(TERB2):c.544dupA(p.Met182AsnfsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,601,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
TERB2
NM_152448.3 frameshift
NM_152448.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.18
Publications
1 publications found
Genes affected
TERB2 (HGNC:28520): (telomere repeat binding bouquet formation protein 2) Predicted to be involved in homologous chromosome pairing at meiosis and meiotic attachment of telomere to nuclear envelope. Predicted to be located in chromosome, telomeric region. Predicted to be active in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]
TERB2 Gene-Disease associations (from GenCC):
- spermatogenic failure 59Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 7 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.178 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-44978508-C-CA is Pathogenic according to our data. Variant chr15-44978508-C-CA is described in ClinVar as Pathogenic. ClinVar VariationId is 1326958.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_152448.3. 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 |
|---|---|---|---|---|---|---|---|---|---|
| TERB2 | NM_152448.3 | MANE Select | c.544dupA | p.Met182AsnfsTer10 | frameshift | Exon 7 of 7 | NP_689661.1 | Q8NHR7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TERB2 | ENST00000340827.4 | TSL:1 MANE Select | c.544dupA | p.Met182AsnfsTer10 | frameshift | Exon 7 of 7 | ENSP00000340644.3 | Q8NHR7 | |
| TERB2 | ENST00000557864.1 | TSL:3 | n.*541dupA | non_coding_transcript_exon | Exon 6 of 6 | ENSP00000452951.1 | H0YKV2 | ||
| TERB2 | ENST00000559137.5 | TSL:5 | n.*510dupA | non_coding_transcript_exon | Exon 6 of 6 | ENSP00000454013.1 | H0YNH3 |
Frequencies
GnomAD3 genomes 0.0000264 AC: 4AN: 151802Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
151802
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000131 AC: 19AN: 1450056Hom.: 0 Cov.: 30 AF XY: 0.00000971 AC XY: 7AN XY: 721068 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
19
AN:
1450056
Hom.:
Cov.:
30
AF XY:
AC XY:
7
AN XY:
721068
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33192
American (AMR)
AF:
AC:
0
AN:
43748
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25776
East Asian (EAS)
AF:
AC:
0
AN:
39466
South Asian (SAS)
AF:
AC:
0
AN:
83408
European-Finnish (FIN)
AF:
AC:
0
AN:
52904
Middle Eastern (MID)
AF:
AC:
0
AN:
5684
European-Non Finnish (NFE)
AF:
AC:
19
AN:
1106068
Other (OTH)
AF:
AC:
0
AN:
59810
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000222045), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.362
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
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<30
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Age
GnomAD4 genome 0.0000264 AC: 4AN: 151802Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74106 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
151802
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74106
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41302
American (AMR)
AF:
AC:
0
AN:
15256
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5196
South Asian (SAS)
AF:
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
AC:
0
AN:
10504
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
4
AN:
67962
Other (OTH)
AF:
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
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65-70
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Spermatogenic failure 59 (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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