rs6855142

Variant names:

• chr4-139966886-G-A
• rs6855142
• NM_018717.5:c.469-75919C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 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.469-75919C>T		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.469-75919C>T		intron	N/A	ENSP00000421180.1
	MAML3	ENST00000502696.1	TSL:2	c.108+185974C>T		intron	N/A	ENSP00000422783.1

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

African (AFR) AF: 0.477 AC: 19759 AN: 41408

American (AMR) AF: 0.514 AC: 7857 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3187 AN: 5158

South Asian (SAS) AF: 0.546 AC: 2628 AN: 4812

European-Finnish (FIN) AF: 0.195 AC: 2059 AN: 10536

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20118 AN: 67938

Other (OTH) AF: 0.389 AC: 821 AN: 2108

Alfa AF: 0.347 Hom.: 1685

Bravo AF: 0.410

Asia WGS AF: 0.573 AC: 1991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.56
PhyloP100		-0.30
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: rs6855142; hg19: chr4-140888040;