Variant 5-179733401-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014757.5(MAML1):c.289G>C(p.Gly97Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,151,656 control chromosomes in the GnomAD database, including 1,354 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.038 ( 172 hom., cov: 33)

Exomes 𝑓: 0.048 ( 1182 hom. )

Consequence

MAML1
NM_014757.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.20

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027258992).

BP6

Variant 5-179733401-G-C is Benign according to our data. Variant chr5-179733401-G-C is described in ClinVar as [Benign]. Clinvar id is 769312.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAML1	NM_014757.5 linkuse as main transcript	c.289G>C	p.Gly97Arg	missense_variant	1/5	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.289G>C	p.Gly97Arg	missense_variant	1/5	1	NM_014757.5	ENSP00000292599.3		Q92585

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5762

AN:

150910

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00908

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0362

Gnomad ASJ

AF:

0.0866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0203

Gnomad FIN

AF:

0.0624

Gnomad MID

AF:

0.0637

Gnomad NFE

AF:

0.0528

Gnomad OTH

AF:

0.0488

GnomAD3 exomes

AF:

0.0179

AC:

AN:

Hom.:

AF XY:

0.0385

AC XY:

AN XY:

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0278

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0479

AC:

47924

AN:

1000638

Hom.:

1182

Cov.:

AF XY:

0.0483

AC XY:

23003

AN XY:

476732

show subpopulations

Gnomad4 AFR exome

AF:

0.00626

Gnomad4 AMR exome

AF:

0.0280

Gnomad4 ASJ exome

AF:

0.0865

Gnomad4 EAS exome

AF:

0.000238

Gnomad4 SAS exome

AF:

0.0187

Gnomad4 FIN exome

AF:

0.0566

Gnomad4 NFE exome

AF:

0.0498

Gnomad4 OTH exome

AF:

0.0491

GnomAD4 genome

AF:

0.0382

AC:

5763

AN:

151018

Hom.:

172

Cov.:

AF XY:

0.0386

AC XY:

2847

AN XY:

73808

show subpopulations

Gnomad4 AFR

AF:

0.00905

Gnomad4 AMR

AF:

0.0361

Gnomad4 ASJ

AF:

0.0866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.0624

Gnomad4 NFE

AF:

0.0528

Gnomad4 OTH

AF:

0.0488

Alfa

AF:

0.0456

Hom.:

Bravo

AF:

0.0353

TwinsUK

AF:

0.0529

AC:

196

ALSPAC

AF:

0.0451

AC:

174

ExAC

AF:

0.00369

AC:

155

Asia WGS

AF:

0.0120

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.012

FATHMM_MKL

Benign

0.15

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.63

REVEL

Benign

0.027

Sift

Uncertain

0.015

Sift4G

Benign

0.12

Polyphen

0.0070

Vest4

0.16

MPC

2.1

ClinPred

0.27

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.28

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