chr4-139889909-TTGCTGCTGC-T

Variant names:

• chr4-139889909-TTGCTGCTGC-T
• rs58015886
• NM_018717.5:c.1518_1526delGCAGCAGCA

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.00

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5	c.1518_1526delGCAGCAGCA	p.Gln507_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.1518_1526delGCAGCAGCA	p.Gln507_Gln509del	disruptive_inframe_deletion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1	c.1518_1526delGCAGCAGCA	p.Gln507_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.1518_1526delGCAGCAGCA	p.Gln507_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1
MAML3	ENST00000502696.1	c.109-159251_109-159243delGCAGCAGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.0773 AC: 3689 AN: 47722 Hom.: 138 Cov.: 0

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

GnomAD3 exomes AF: 0.00916 AC: 1567 AN: 171060 Hom.: 48 AF XY: 0.00801 AC XY: 750 AN XY: 93608

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 SAS exome AF: 0.00426

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

Gnomad4 AFR exome AF: 0.0773

Gnomad4 AMR exome AF: 0.00743

Gnomad4 ASJ exome AF: 0.00145

Gnomad4 EAS exome AF: 0.00956

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.000325

Gnomad4 NFE exome AF: 0.00248

Gnomad4 OTH exome AF: 0.00820

GnomAD4 genome AF: 0.0773 AC: 3696 AN: 47810 Hom.: 138 Cov.: 0 AF XY: 0.0733 AC XY: 1721 AN XY: 23484

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.0254

Gnomad4 ASJ AF: 0.00896

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.00935

Gnomad4 FIN AF: 0.00120

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0637

ClinVar

Not reported in ClinVar

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;