Genetic Variant MAML3:p.Gln507_Gln509del (chr4-139889909-TTGCTGCTGC-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP3BA1

The NM_018717.5(MAML3):c.1518_1526delGCAGCAGCA(p.Gln507_Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00707 in 1,475,070 control chromosomes in the GnomAD database, including 339 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.077 ( 138 hom., cov: 0)

Exomes 𝑓: 0.0047 ( 201 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: Benign. The variant received -9 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_018717.5

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

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.1518_1526delGCAGCAGCA	p.Gln507_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.1518_1526delGCAGCAGCA	p.Gln507_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000421180.1	Q96JK9
MAML3	ENST00000899537.1		c.1518_1526delGCAGCAGCA	p.Gln507_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENSP00000569596.1
MAML3	ENST00000502696.1	TSL:2	c.109-159251_109-159243delGCAGCAGCA		intron	N/A	ENSP00000422783.1	H0Y920

Frequencies

GnomAD3 genomes

AF:

0.0773

AC:

3689

AN:

47722

Hom.:

138

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.00896

Gnomad EAS

AF:

0.0221

Gnomad SAS

AF:

0.00936

Gnomad FIN

AF:

0.00120

Gnomad MID

AF:

0.0521

Gnomad NFE

AF:

0.0217

Gnomad OTH

AF:

0.0609

GnomAD2 exomes

AF:

0.00916

AC:

1567

AN:

171060

AF XY:

0.00801

show subpopulations

Gnomad AFR exome

AF:

0.0731

Gnomad AMR exome

AF:

0.00947

Gnomad ASJ exome

AF:

0.00274

Gnomad EAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.000335

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.00967

GnomAD4 exome

AF:

0.00471

AC:

6728

AN:

1427260

Hom.:

201

AF XY:

0.00444

AC XY:

3143

AN XY:

707132

show subpopulations

African (AFR)

AF:

0.0773

AC:

2524

AN:

32634

American (AMR)

AF:

0.00743

AC:

324

AN:

43632

Ashkenazi Jewish (ASJ)

AF:

0.00145

AC:

AN:

25458

East Asian (EAS)

AF:

0.00956

AC:

371

AN:

38798

South Asian (SAS)

AF:

0.00301

AC:

255

AN:

84786

European-Finnish (FIN)

AF:

0.000325

AC:

AN:

52382

Middle Eastern (MID)

AF:

0.00484

AC:

AN:

5578

European-Non Finnish (NFE)

AF:

0.00248

AC:

2690

AN:

1085088

Other (OTH)

AF:

0.00820

AC:

483

AN:

58904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

317

634

951

1268

1585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.0773

AC:

3696

AN:

47810

Hom.:

138

Cov.:

AF XY:

0.0733

AC XY:

1721

AN XY:

23484

show subpopulations

African (AFR)

AF:

0.116

AC:

3284

AN:

28418

American (AMR)

AF:

0.0254

AC:

136

AN:

5348

Ashkenazi Jewish (ASJ)

AF:

0.00896

AC:

AN:

670

East Asian (EAS)

AF:

0.0221

AC:

AN:

2310

South Asian (SAS)

AF:

0.00935

AC:

AN:

1284

European-Finnish (FIN)

AF:

0.00120

AC:

AN:

1668

Middle Eastern (MID)

AF:

0.0581

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0217

AC:

159

AN:

7330

Other (OTH)

AF:

0.0637

AC:

AN:

644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

140

280

420

560

700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.00499

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=193/7

polymorphism (auto)

(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