Genetic Variant NM_014757.5:c.390C>T (chr5-179765400-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014757.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML1	NM_014757.5	MANE Select	c.390C>T	p.Tyr130Tyr	synonymous	Exon 2 of 5	NP_055572.1	Q92585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAML1	ENST00000292599.4	TSL:1 MANE Select	c.390C>T	p.Tyr130Tyr	synonymous	Exon 2 of 5	ENSP00000292599.3	Q92585
	MAML1	ENST00000933871.1		c.390C>T	p.Tyr130Tyr	synonymous	Exon 2 of 5	ENSP00000603930.1

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

GnomAD2 exomes

AF:

0.00421

AC:

1057

AN:

251272

AF XY:

0.00434

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 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

African (AFR)

AF:

0.00119

AC:

AN:

33476

American (AMR)

AF:

0.00181

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000719

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00189

AC:

101

AN:

53416

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00906

AC:

10074

AN:

1111936

Other (OTH)

AF:

0.00583

AC:

352

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

556

1112

1669

2225

2781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00485

AC:

738

AN:

152284

Hom.:

Cov.:

AF XY:

0.00443

AC XY:

330

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

41554

American (AMR)

AF:

0.00255

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000622

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00870

AC:

592

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

116

154

193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.14

(source)

DANN

Benign

0.88

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over