rs1531070

chr4-139874173-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• 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/exons	MANE	UniProt
MAML3	NM_018717.5	c.2079+15184C>T		intron_variant		ENST00000509479.6
MAML3	XM_047415929.1	c.2079+15184C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML3	ENST00000509479.6	c.2079+15184C>T		intron_variant		1	NM_018717.5	P1
MAML3	ENST00000502696.1	c.111-143506C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.281

Alfa AF: 0.379 Hom.: 21602

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

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: rs1531070; hg19: chr4-140795327;