4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGC-T
• rs58015886
• NM_018717.5:c.1503_1526delGCAGCAGCAGCAGCAGCAGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_018717.5(MAML3):​c.1503_1526delGCAGCAGCAGCAGCAGCAGCAGCA​(p.Gln502_Gln509del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000328 in 1,476,644 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00030 (1 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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_018717.5
• BS2: High AC in GnomAd4 at 50 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5	c.1503_1526delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln502_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.1503_1526delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln502_Gln509del	disruptive_inframe_deletion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1	c.1503_1526delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln502_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.1503_1526delGCAGCAGCAGCAGCAGCAGCAGCA	p.Gln502_Gln509del	disruptive_inframe_deletion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1
MAML3	ENST00000502696.1	c.109-159266_109-159243delGCAGCAGCAGCAGCAGCAGCAGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.00107 AC: 51 AN: 47822 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000774

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000374

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000865

Gnomad SAS AF: 0.0164

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000545

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000304 AC: 434 AN: 1428734 Hom.: 1 AF XY: 0.000374 AC XY: 265 AN XY: 707954

Gnomad4 AFR exome AF: 0.000305

Gnomad4 AMR exome AF: 0.000136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.00379

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.0000636

Gnomad4 OTH exome AF: 0.000305

GnomAD4 genome AF: 0.00104 AC: 50 AN: 47910 Hom.: 0 Cov.: 0 AF XY: 0.00106 AC XY: 25 AN XY: 23536

Gnomad4 AFR AF: 0.000772

Gnomad4 AMR AF: 0.000373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000866

Gnomad4 SAS AF: 0.0156

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000545

Gnomad4 OTH AF: 0.00

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;