Variant 5-179765400-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014757.5(MAML1):c.390C>T(p.Tyr130Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00714 in 1,614,054 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 52 hom. )

Consequence

MAML1
NM_014757.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

Variant links:

Genes affected

MAML1 (HGNC:13632): (mastermind like transcriptional coactivator 1) This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway. [provided by RefSeq, Jul 2008]

MAML1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 5-179765400-C-T is Benign according to our data. Variant chr5-179765400-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656135.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.35 with no splicing effect.

BS2

High AC in GnomAd4 at 738 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML1	NM_014757.5 linkuse as main transcript	c.390C>T	p.Tyr130Tyr	synonymous_variant	2/5	ENST00000292599.4	NP_055572.1	Q92585

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAML1	ENST00000292599.4 linkuse as main transcript	c.390C>T	p.Tyr130Tyr	synonymous_variant	2/5	1	NM_014757.5	ENSP00000292599.3		Q92585

Frequencies

GnomAD3 genomes

AF:

0.00485

AC:

738

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00870

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00421

AC:

1057

AN:

251272

Hom.:

AF XY:

0.00434

AC XY:

589

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00179

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000915

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.00761

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00738

AC:

10782

AN:

1461770

Hom.:

Cov.:

AF XY:

0.00706

AC XY:

5135

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00119

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.00260

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.00189

Gnomad4 NFE exome

AF:

0.00906

Gnomad4 OTH exome

AF:

0.00583

GnomAD4 genome

AF:

0.00485

AC:

738

AN:

152284

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00183

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00870

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00671

Hom.:

Bravo

AF:

0.00451

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00834

EpiControl

AF:

0.00705

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

MAML1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.14

DANN

Benign

0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over