4-139889909-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC-TTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTGC

Variant names:

• chr4-139889909-T-TTGCTGCTGC
• rs58015886
• NM_018717.5:c.1518_1526dupGCAGCAGCA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018717.5(MAML3):​c.1518_1526dupGCAGCAGCA​(p.Gln507_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 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00031 (10 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAML3 NM_018717.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 74 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5	c.1518_1526dupGCAGCAGCA	p.Gln507_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5	ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.1518_1526dupGCAGCAGCA	p.Gln507_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5		XP_047271885.1
MAML3	XM_047415930.1	c.1518_1526dupGCAGCAGCA	p.Gln507_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	c.1518_1526dupGCAGCAGCA	p.Gln507_Gln509dup	disruptive_inframe_insertion	Exon 2 of 5	1	NM_018717.5	ENSP00000421180.1
MAML3	ENST00000502696.1	c.109-159251_109-159243dupGCAGCAGCA		intron_variant	Intron 1 of 3	2		ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 74 AN: 47816 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000915

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000374

Gnomad ASJ AF: 0.00746

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00480

Gnomad MID AF: 0.0521

Gnomad NFE AF: 0.00368

Gnomad OTH AF: 0.00155

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000310 AC: 443 AN: 1428560 Hom.: 10 Cov.: 0 AF XY: 0.000318 AC XY: 225 AN XY: 707860

Gnomad4 AFR exome AF: 0.000550

Gnomad4 AMR exome AF: 0.000295

Gnomad4 ASJ exome AF: 0.00126

Gnomad4 EAS exome AF: 0.000129

Gnomad4 SAS exome AF: 0.0000352

Gnomad4 FIN exome AF: 0.000534

Gnomad4 NFE exome AF: 0.000292

Gnomad4 OTH exome AF: 0.000407

GnomAD4 genome AF: 0.00154 AC: 74 AN: 47904 Hom.: 0 Cov.: 0 AF XY: 0.00153 AC XY: 36 AN XY: 23530

Gnomad4 AFR AF: 0.000912

Gnomad4 AMR AF: 0.000373

Gnomad4 ASJ AF: 0.00746

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00480

Gnomad4 NFE AF: 0.00368

Gnomad4 OTH AF: 0.00154

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;