Variant 5-179765579-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014757.5(MAML1):c.569G>A(p.Arg190His) variant causes a missense change. The variant allele was found at a frequency of 0.00239 in 1,614,144 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 11 hom. )

Consequence

MAML1
NM_014757.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.17

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065487027).

BP6

Variant 5-179765579-G-A is Benign according to our data. Variant chr5-179765579-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd at 336 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML1	NM_014757.5 linkuse as main transcript	c.569G>A	p.Arg190His	missense_variant	2/5	ENST00000292599.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAML1	ENST00000292599.4 linkuse as main transcript	c.569G>A	p.Arg190His	missense_variant	2/5	1	NM_014757.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

336

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00236

AC:

592

AN:

251308

Hom.:

AF XY:

0.00253

AC XY:

344

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00291

Gnomad NFE exome

AF:

0.00334

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00241

AC:

3519

AN:

1461856

Hom.:

Cov.:

AF XY:

0.00242

AC XY:

1758

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.00517

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.00238

Gnomad4 NFE exome

AF:

0.00263

Gnomad4 OTH exome

AF:

0.00268

GnomAD4 genome

AF:

0.00221

AC:

336

AN:

152288

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00306

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00281

Hom.:

Bravo

AF:

0.00239

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00314

AC:

ExAC

AF:

0.00227

AC:

276

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00360

EpiControl

AF:

0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 26, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	MAML1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.23

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.058

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.016

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.95

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.23

REVEL

Benign

0.061

Sift

Benign

0.19

Sift4G

Benign

0.14

Polyphen

0.0050

Vest4

0.13

MVP

0.30

MPC

0.23

ClinPred

0.031

GERP RS

4.9

Varity_R

0.067

gMVP

0.20

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