4-139889909-T-TTGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018717.5(MAML3):c.1526_1527insGCA(p.Gln509dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.049 (25 hom., cov: 0)
  • Exomes 𝑓: 0.019 (274 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAML3 NM_018717.5 inframe_insertion
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-139889909-T-TTGC is Benign according to our data. Variant chr4-139889909-T-TTGC is described in ClinVar as [Benign]. Clinvar id is 770352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML3	NM_018717.5	c.1526_1527insGCA	p.Gln509dup	inframe_insertion	2/5	ENST00000509479.6
MAML3	XM_047415929.1	c.1526_1527insGCA	p.Gln509dup	inframe_insertion	2/5
MAML3	XM_047415930.1	c.1526_1527insGCA	p.Gln509dup	inframe_insertion	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML3	ENST00000509479.6	c.1526_1527insGCA	p.Gln509dup	inframe_insertion	2/5	1	NM_018717.5	P1
MAML3	ENST00000502696.1	c.111-159243_111-159242insGCA		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0494 AC: 2360 AN: 47766 Hom.: 26 Cov.: 0

Gnomad AFR AF: 0.00947

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.00303

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.0521

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.0543

GnomAD3 exomes AF: 0.0122 AC: 2083 AN: 171060 Hom.: 1 AF XY: 0.0122 AC XY: 1146 AN XY: 93608

Gnomad AFR exome AF: 0.00426

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.0204

Gnomad EAS exome AF: 0.00155

Gnomad SAS exome AF: 0.00768

Gnomad FIN exome AF: 0.00556

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0191

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0191 AC: 27280 AN: 1425548 Hom.: 274 Cov.: 0 AF XY: 0.0190 AC XY: 13405 AN XY: 706376

Gnomad4 AFR exome AF: 0.00452

Gnomad4 AMR exome AF: 0.00933

Gnomad4 ASJ exome AF: 0.0174

Gnomad4 EAS exome AF: 0.00108

Gnomad4 SAS exome AF: 0.00740

Gnomad4 FIN exome AF: 0.00722

Gnomad4 NFE exome AF: 0.0223

Gnomad4 OTH exome AF: 0.0173

GnomAD4 genome AF: 0.0493 AC: 2357 AN: 47854 Hom.: 25 Cov.: 0 AF XY: 0.0449 AC XY: 1055 AN XY: 23504

Gnomad4 AFR AF: 0.00944

Gnomad4 AMR AF: 0.0368

Gnomad4 ASJ AF: 0.0940

Gnomad4 EAS AF: 0.00303

Gnomad4 SAS AF: 0.0374

Gnomad4 FIN AF: 0.0420

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.0540

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58015886; hg19: chr4-140811063;