rs6855142

Positions:

• chr4-139966886-G-A
• chr4-139966886-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018717.5(MAML3):​c.469-75919C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,908 control chromosomes in the GnomAD database, including 12,222 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 0.38 (12222 hom., cov: 32)
• Consequence: MAML3 NM_018717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML3	NM_018717.5	c.469-75919C>T		intron_variant		ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.469-75919C>T		intron_variant			XP_047271885.1
MAML3	XM_047415930.1	c.469-75919C>T		intron_variant			XP_047271886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAML3	ENST00000509479.6	c.469-75919C>T		intron_variant		1	NM_018717.5	ENSP00000421180	P1
MAML3	ENST00000502696.1	c.110+185974C>T		intron_variant		2		ENSP00000422783

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57991 AN: 151790 Hom.: 12200 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.382 AC: 58059 AN: 151908 Hom.: 12222 Cov.: 32 AF XY: 0.386 AC XY: 28676 AN XY: 74236

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.195

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.389

Alfa AF: 0.343 Hom.: 1598

Bravo AF: 0.410

Asia WGS AF: 0.573 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.56

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: rs6855142; hg19: chr4-140888040;