Genetic Variant MAML3:p.Gln501_Gln509del (chr4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGC-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3BS2

The NM_018717.5(MAML3):c.1500_1526delGCAGCAGCAGCAGCAGCAGCAGCAGCA(p.Gln501_Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0000725 in 1,476,654 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.00021 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000068 ( 0 hom. )

Consequence

MAML3
NM_018717.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Publications

3 publications found

Variant links:

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]

MAML3 links:

ENSG00000294637 (HGNC:):

ENSG00000294637 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_018717.5

BS2

High AC in GnomAd4 at 10 AD gene.

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_1526delGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln501_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	NP_061187.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAML3	ENST00000509479.6	TSL:1 MANE Select	c.1500_1526delGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln501_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000421180.1	Q96JK9
MAML3	ENST00000899537.1		c.1500_1526delGCAGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln501_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000569596.1
MAML3	ENST00000502696.1	TSL:2	c.109-159269_109-159243delGCAGCAGCAGCAGCAGCAGCAGCAGCA		intron	N/A	ENSP00000422783.1	H0Y920

Frequencies

GnomAD3 genomes

AF:

0.000209

AC:

AN:

47822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000433

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000273

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000679

AC:

AN:

1428744

Hom.:

AF XY:

0.0000735

AC XY:

AN XY:

707956

show subpopulations

African (AFR)

AF:

0.000305

AC:

AN:

32738

American (AMR)

AF:

0.000136

AC:

AN:

44096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25486

East Asian (EAS)

AF:

0.000309

AC:

AN:

38820

South Asian (SAS)

AF:

0.0000352

AC:

AN:

85316

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.0000571

AC:

AN:

1085330

Other (OTH)

AF:

0.0000678

AC:

AN:

58958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000209

AC:

AN:

47910

Hom.:

Cov.:

AF XY:

0.0000850

AC XY:

AN XY:

23536

show subpopulations

African (AFR)

AF:

0.000246

AC:

AN:

28500

American (AMR)

AF:

0.00

AC:

AN:

5358

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

670

East Asian (EAS)

AF:

0.000433

AC:

AN:

2310

South Asian (SAS)

AF:

0.00

AC:

AN:

1284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1668

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000273

AC:

AN:

7334

Other (OTH)

AF:

0.00

AC:

AN:

648

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=180/20

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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