Variant 5-179765340-A-G 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.330A>G(p.Thr110=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,596,726 control chromosomes in the GnomAD database, including 52 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: 0.0073 ( 50 hom. )

Consequence

MAML1
NM_014757.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 5-179765340-A-G is Benign according to our data. Variant chr5-179765340-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656134.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.36 with no splicing effect.

BS2

High AC in GnomAd4 at 731 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAML1	NM_014757.5 linkuse as main transcript	c.330A>G	p.Thr110=	synonymous_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.330A>G	p.Thr110=	synonymous_variant	2/5	1	NM_014757.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00480

AC:

731

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00169

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00869

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00426

AC:

1011

AN:

237142

Hom.:

AF XY:

0.00433

AC XY:

556

AN XY:

128382

show subpopulations

Gnomad AFR exome

AF:

0.00181

Gnomad AMR exome

AF:

0.00166

Gnomad ASJ exome

AF:

0.00206

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000956

Gnomad FIN exome

AF:

0.00133

Gnomad NFE exome

AF:

0.00762

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00734

AC:

10604

AN:

1444376

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

5050

AN XY:

718180

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.00261

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000728

Gnomad4 FIN exome

AF:

0.00190

Gnomad4 NFE exome

AF:

0.00897

Gnomad4 OTH exome

AF:

0.00581

GnomAD4 genome

AF:

0.00480

AC:

731

AN:

152350

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

325

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00169

Gnomad4 NFE

AF:

0.00869

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00625

Hom.:

Bravo

AF:

0.00447

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

-0.73

CADD

Benign

0.44

DANN

Benign

0.62

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