Genetic Variant MAML3:p.Gln506_Gln509dup (chr4-139889909-T-TTGCTGCTGCTGC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018717.5(MAML3):c.1515_1526dupGCAGCAGCAGCA(p.Gln506_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 0.00050 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000065 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

MAML3
NM_018717.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.616

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5 link	c.1515_1526dupGCAGCAGCAGCA	p.Gln506_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5	ENST00000509479.6	NP_061187.3	Q96JK9Q9NPV6
MAML3	XM_047415929.1 link	c.1515_1526dupGCAGCAGCAGCA	p.Gln506_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1 link	c.1515_1526dupGCAGCAGCAGCA	p.Gln506_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 link	c.1515_1526dupGCAGCAGCAGCA	p.Gln506_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1		Q96JK9
MAML3	ENST00000502696.1 link	c.109-159254_109-159243dupGCAGCAGCAGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1		H0Y920

Frequencies

GnomAD3 genomes

AF:

0.000502

AC:

AN:

47822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000865

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00123

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000651

AC:

AN:

1428710

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

707940

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

Gnomad4 AMR exome

AF:

0.0000454

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000412

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000763

Gnomad4 NFE exome

AF:

0.0000599

Gnomad4 OTH exome

AF:

0.0000848

GnomAD4 genome

AF:

0.000502

AC:

AN:

47822

Hom.:

Cov.:

AF XY:

0.000554

AC XY:

AN XY:

23456

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000865

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over