rs1531070

Variant names:

• chr4-139874173-G-A
• rs1531070
• NM_018717.5:c.2079+15184C>T

Variant summary

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

The NM_018717.5(MAML3):​c.2079+15184C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,000 control chromosomes in the GnomAD database, including 8,301 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 0.30 (8301 hom., cov: 32)
• Consequence: MAML3 NM_018717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166
• Publications: 21 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]

ENSG00000294637 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAML3	NM_018717.5	c.2079+15184C>T		intron_variant	Intron 2 of 4	ENST00000509479.6	NP_061187.3
MAML3	XM_047415929.1	c.2079+15184C>T		intron_variant	Intron 2 of 4		XP_047271885.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAML3	ENST00000509479.6	c.2079+15184C>T		intron_variant	Intron 2 of 4	1	NM_018717.5	ENSP00000421180.1
MAML3	ENST00000502696.1	c.109-143506C>T		intron_variant	Intron 1 of 3	2		ENSP00000422783.1
ENSG00000294637	ENST00000724876.1	n.182+304G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45038 AN: 151882 Hom.: 8301 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.296 AC: 45040 AN: 152000 Hom.: 8301 Cov.: 32 AF XY: 0.293 AC XY: 21777 AN XY: 74310

African (AFR) AF: 0.104 AC: 4301 AN: 41480

American (AMR) AF: 0.251 AC: 3838 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1147 AN: 3470

East Asian (EAS) AF: 0.124 AC: 639 AN: 5174

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4812

European-Finnish (FIN) AF: 0.465 AC: 4896 AN: 10536

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27951 AN: 67940

Other (OTH) AF: 0.281 AC: 593 AN: 2112

Alfa AF: 0.371 Hom.: 43956

Bravo AF: 0.271

Asia WGS AF: 0.173 AC: 600 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.3
DANN	Benign	0.77
PhyloP100		0.17
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: rs1531070; hg19: chr4-140795327;