rs1584783

Variant names:

• chr4-139739238-T-C
• rs1584783
• NM_018717.5:c.2080-8571A>G

Variant summary

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

The NM_018717.5(MAML3):​c.2080-8571A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,108 control chromosomes in the GnomAD database, including 19,125 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 0.49 (19125 hom., cov: 32)
• Consequence: MAML3 NM_018717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• 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]

MGST2 (HGNC:7063): (microsomal glutathione S-transferase 2) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes a protein which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. [provided by RefSeq, Feb 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.623 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.2080-8571A>G		intron	N/A	NP_061187.3
	MGST2	NM_001204366.2		c.*49-974T>C		intron	N/A	NP_001191295.1
	MGST2	NM_001204367.2		c.*49-974T>C		intron	N/A	NP_001191296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML3	ENST00000509479.6	TSL:1 MANE Select	c.2080-8571A>G		intron	N/A	ENSP00000421180.1
	MGST2	ENST00000515137.5	TSL:1	n.480-974T>C		intron	N/A
	MAML3	ENST00000502696.1	TSL:2	c.109-8571A>G		intron	N/A	ENSP00000422783.1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73822 AN: 151990 Hom.: 19137 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.655

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.485 AC: 73839 AN: 152108 Hom.: 19125 Cov.: 32 AF XY: 0.488 AC XY: 36308 AN XY: 74370

African (AFR) AF: 0.312 AC: 12960 AN: 41480

American (AMR) AF: 0.411 AC: 6277 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.655 AC: 2273 AN: 3470

East Asian (EAS) AF: 0.521 AC: 2690 AN: 5166

South Asian (SAS) AF: 0.642 AC: 3097 AN: 4826

European-Finnish (FIN) AF: 0.586 AC: 6194 AN: 10574

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38511 AN: 67994

Other (OTH) AF: 0.512 AC: 1082 AN: 2112

Alfa AF: 0.543 Hom.: 17060

Bravo AF: 0.463

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.28
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: rs1584783; hg19: chr4-140660392;