4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr4-139889909-TTGC-T
• rs58015886
• NM_018717.5:c.1524_1526delGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_018717.5(MAML3):​c.1524_1526delGCA​(p.Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.0257 in 1,459,490 control chromosomes in the GnomAD database, including 1,293 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (832 hom., cov: 0)
  • Exomes 𝑓: 0.019 (461 hom.)
• Consequence: MAML3 NM_018717.5 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5	c.1524_1526delGCA	p.Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.1524_1526delGCA	p.Gln509del	disruptive_inframe_deletion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1	c.1524_1526delGCA	p.Gln509del	disruptive_inframe_deletion	Exon 2 of 3		XP_047271886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML3	ENST00000509479.6	c.1524_1526delGCA	p.Gln509del	disruptive_inframe_deletion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1
MAML3	ENST00000502696.1	c.109-159245_109-159243delGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 10196 AN: 47500 Hom.: 830 Cov.: 0

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0719

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.128

Gnomad NFE AF: 0.0592

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.0412 AC: 7045 AN: 171060 Hom.: 171 AF XY: 0.0374 AC XY: 3503 AN XY: 93608

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.0537

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.197

Gnomad SAS exome AF: 0.0322

Gnomad FIN exome AF: 0.0416

Gnomad NFE exome AF: 0.00560

Gnomad OTH exome AF: 0.0366

GnomAD4 exome AF: 0.0193 AC: 27266 AN: 1411902 Hom.: 461 AF XY: 0.0190 AC XY: 13263 AN XY: 699610

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.0452

Gnomad4 ASJ exome AF: 0.0113

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.0284

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.00570

Gnomad4 OTH exome AF: 0.0372

GnomAD4 genome AF: 0.215 AC: 10214 AN: 47588 Hom.: 832 Cov.: 0 AF XY: 0.217 AC XY: 5073 AN XY: 23374

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.0719

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;