4-139816600-C-T

Variant summary

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

The NM_018717.5(MAML3):c.2079+72757G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 152,094 control chromosomes in the GnomAD database, including 57,871 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 0.87 (57871 hom., cov: 30)
• Consequence: MAML3 NM_018717.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.975

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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML3	NM_018717.5	c.2079+72757G>A		intron_variant		ENST00000509479.6
MAML3	XM_047415929.1	c.2079+72757G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML3	ENST00000509479.6	c.2079+72757G>A		intron_variant		1	NM_018717.5	P1
MAML3	ENST00000502696.1	c.111-85933G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132389 AN: 151976 Hom.: 57815 Cov.: 30

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.839

Gnomad OTH AF: 0.857

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

GnomAD4 genome AF: 0.871 AC: 132503 AN: 152094 Hom.: 57871 Cov.: 30 AF XY: 0.870 AC XY: 64658 AN XY: 74324

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.824

Gnomad4 SAS AF: 0.895

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.858

Alfa AF: 0.854 Hom.: 25241

Bravo AF: 0.874

Asia WGS AF: 0.885 AC: 3077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.96
Dann	Benign	0.81

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: rs795995; hg19: chr4-140737754;