Genetic Variant NM_018717.5:c.1512_1526dupGCAGCAGCAGCAGCA (chr4-139889909-T-TTGCTGCTGCTGCTGC) – 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.1512_1526dupGCAGCAGCAGCAGCA(p.Gln505_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 0.000084 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000019 ( 0 hom. )

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 GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5 link	c.1512_1526dupGCAGCAGCAGCAGCA	p.Gln505_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5	ENST00000509479.6	NP_061187.3	Q96JK9Q9NPV6
MAML3	XM_047415929.1 link	c.1512_1526dupGCAGCAGCAGCAGCA	p.Gln505_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1 link	c.1512_1526dupGCAGCAGCAGCAGCA	p.Gln505_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.1512_1526dupGCAGCAGCAGCAGCA	p.Gln505_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1		Q96JK9
MAML3	ENST00000502696.1 link	c.109-159257_109-159243dupGCAGCAGCAGCAGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1		H0Y920

Frequencies

GnomAD3 genomes

AF:

0.0000836

AC:

AN:

47822

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000780

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000273

Gnomad OTH

AF:

0.00155

GnomAD4 exome

AF:

0.0000189

AC:

AN:

1428740

Hom.:

Cov.:

AF XY:

0.0000198

AC XY:

AN XY:

707954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000227

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000206

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.0000339

GnomAD4 genome

AF:

0.0000836

AC:

AN:

47822

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

23456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000780

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000273

Gnomad4 OTH

AF:

0.00155

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.

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