rs4863687

Variant names:

• chr4-139757127-C-T
• rs4863687
• NM_018717.5:c.2080-26460G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018717.5(MAML3):​c.2080-26460G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,938 control chromosomes in the GnomAD database, including 4,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (4698 hom., cov: 30)
• Consequence: MAML3 NM_018717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018717.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML3	NM_018717.5	MANE Select	c.2080-26460G>A		intron	N/A	NP_061187.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML3	ENST00000509479.6	TSL:1 MANE Select	c.2080-26460G>A		intron	N/A	ENSP00000421180.1
	MAML3	ENST00000502696.1	TSL:2	c.109-26460G>A		intron	N/A	ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37117 AN: 151818 Hom.: 4696 Cov.: 30

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.225

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37139 AN: 151938 Hom.: 4698 Cov.: 30 AF XY: 0.247 AC XY: 18331 AN XY: 74268

African (AFR) AF: 0.209 AC: 8667 AN: 41420

American (AMR) AF: 0.290 AC: 4433 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1201 AN: 5156

South Asian (SAS) AF: 0.202 AC: 975 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3551 AN: 10538

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17052 AN: 67960

Other (OTH) AF: 0.224 AC: 472 AN: 2110

Alfa AF: 0.246 Hom.: 20413

Bravo AF: 0.240

Asia WGS AF: 0.169 AC: 588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.63
PhyloP100		0.046
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4863687; hg19: chr4-140678281;