rs1584783

Positions:

• chr4-139739238-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML3	NM_018717.5	c.2080-8571A>G		intron_variant		ENST00000509479.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML3	ENST00000509479.6	c.2080-8571A>G		intron_variant		1	NM_018717.5	P1
MGST2	ENST00000515137.5	n.480-974T>C		intron_variant, non_coding_transcript_variant		1
MAML3	ENST00000502696.1	c.111-8571A>G		intron_variant		2
MGST2	ENST00000616265.4	c.*49-974T>C		intron_variant		4		P1

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

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.411

Gnomad4 ASJ AF: 0.655

Gnomad4 EAS AF: 0.521

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.566

Gnomad4 OTH AF: 0.512

Alfa AF: 0.547 Hom.: 12767

Bravo AF: 0.463

Asia WGS AF: 0.565 AC: 1964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs1584783; hg19: chr4-140660392;