4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_018717.5(MAML3):c.1521_1526dupGCAGCA(p.Gln508_Gln509dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0039 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0012 ( 36 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
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 made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 186 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAML3 | NM_018717.5 | c.1521_1526dupGCAGCA | p.Gln508_Gln509dup | disruptive_inframe_insertion | Exon 2 of 5 | ENST00000509479.6 | NP_061187.3 | |
MAML3 | XM_047415929.1 | c.1521_1526dupGCAGCA | p.Gln508_Gln509dup | disruptive_inframe_insertion | Exon 2 of 5 | XP_047271885.1 | ||
MAML3 | XM_047415930.1 | c.1521_1526dupGCAGCA | p.Gln508_Gln509dup | disruptive_inframe_insertion | Exon 2 of 3 | XP_047271886.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAML3 | ENST00000509479.6 | c.1521_1526dupGCAGCA | p.Gln508_Gln509dup | disruptive_inframe_insertion | Exon 2 of 5 | 1 | NM_018717.5 | ENSP00000421180.1 | ||
MAML3 | ENST00000502696.1 | c.109-159248_109-159243dupGCAGCA | intron_variant | Intron 1 of 3 | 2 | ENSP00000422783.1 |
Frequencies
GnomAD3 genomes AF: 0.00385 AC: 184AN: 47818Hom.: 0 Cov.: 0
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00125 AC: 1782AN: 1428132Hom.: 36 Cov.: 0 AF XY: 0.00118 AC XY: 833AN XY: 707644
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GnomAD4 genome AF: 0.00388 AC: 186AN: 47906Hom.: 0 Cov.: 0 AF XY: 0.00353 AC XY: 83AN XY: 23534
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Not reported inComputational scores
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at