4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_018717.5(MAML3):c.1500_1526dupGCAGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln501_Gln509dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000021 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000042 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
MAML3
NM_018717.5 disruptive_inframe_insertion
NM_018717.5 disruptive_inframe_insertion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.616
Publications
3 publications found
Genes affected
MAML3 (HGNC:16272): (mastermind like transcriptional coactivator 3) Enables transcription coactivator activity. Involved in Notch signaling pathway and positive regulation of transcription by RNA polymerase II. Located in nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_018717.5
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_018717.5. 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 |
|---|---|---|---|---|---|---|---|---|---|
| MAML3 | NM_018717.5 | MANE Select | c.1500_1526dupGCAGCAGCAGCAGCAGCAGCAGCAGCA | p.Gln501_Gln509dup | disruptive_inframe_insertion | Exon 2 of 5 | NP_061187.3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MAML3 | ENST00000509479.6 | TSL:1 MANE Select | c.1500_1526dupGCAGCAGCAGCAGCAGCAGCAGCAGCA | p.Gln501_Gln509dup | disruptive_inframe_insertion | Exon 2 of 5 | ENSP00000421180.1 | Q96JK9 | |
| MAML3 | ENST00000899537.1 | c.1500_1526dupGCAGCAGCAGCAGCAGCAGCAGCAGCA | p.Gln501_Gln509dup | disruptive_inframe_insertion | Exon 2 of 5 | ENSP00000569596.1 | |||
| MAML3 | ENST00000502696.1 | TSL:2 | c.109-159269_109-159243dupGCAGCAGCAGCAGCAGCAGCAGCAGCA | intron | N/A | ENSP00000422783.1 | H0Y920 |
Frequencies
GnomAD3 genomes 0.0000209 AC: 1AN: 47822Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
47822
Hom.:
Cov.:
0
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 Data not reliable, filtered out with message: AS_VQSR AF: 0.00000420 AC: 6AN: 1428744Hom.: 0 Cov.: 0 AF XY: 0.00000283 AC XY: 2AN XY: 707956 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
6
AN:
1428744
Hom.:
Cov.:
0
AF XY:
AC XY:
2
AN XY:
707956
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:
32738
American (AMR)
AF:
AC:
0
AN:
44096
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25486
East Asian (EAS)
AF:
AC:
5
AN:
38820
South Asian (SAS)
AF:
AC:
1
AN:
85316
European-Finnish (FIN)
AF:
AC:
0
AN:
52410
Middle Eastern (MID)
AF:
AC:
0
AN:
5590
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1085330
Other (OTH)
AF:
AC:
0
AN:
58958
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000669465), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.317
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 0.0000209 AC: 1AN: 47822Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 23456 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
47822
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
23456
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
28408
American (AMR)
AF:
AC:
0
AN:
5354
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
670
East Asian (EAS)
AF:
AC:
0
AN:
2312
South Asian (SAS)
AF:
AC:
0
AN:
1282
European-Finnish (FIN)
AF:
AC:
0
AN:
1668
Middle Eastern (MID)
AF:
AC:
0
AN:
96
European-Non Finnish (NFE)
AF:
AC:
0
AN:
7336
Other (OTH)
AF:
AC:
0
AN:
644
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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