Genetic Variant NM_001393504.1:c.327C>T (chr19-18122679-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001393504.1(MAST3):c.327C>T(p.Asp109Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,612,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

MAST3
NM_001393504.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.246

Publications

0 publications found

Variant links:

Genes affected

MAST3 (HGNC:19036): (microtubule associated serine/threonine kinase 3) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in cytoskeleton organization; intracellular signal transduction; and peptidyl-serine phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAST3 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy 108
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

MAST3 links:

ENSG00000297168 (HGNC:):

ENSG00000297168 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 19-18122679-C-T is Benign according to our data. Variant chr19-18122679-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3358337.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.246 with no splicing effect.

BS2

High AC in GnomAd4 at 37 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393504.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST3	NM_001393504.1	MANE Select	c.327C>T	p.Asp109Asp	synonymous	Exon 6 of 28	NP_001380433.1	A0A8I5KST9
MAST3	NM_001393501.1		c.351C>T	p.Asp117Asp	synonymous	Exon 7 of 29	NP_001380430.1
MAST3	NM_001393502.1		c.330C>T	p.Asp110Asp	synonymous	Exon 6 of 28	NP_001380431.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST3	ENST00000687212.1	MANE Select	c.327C>T	p.Asp109Asp	synonymous	Exon 6 of 28	ENSP00000509890.1	A0A8I5KST9
MAST3	ENST00000262811.10	TSL:1	c.240C>T	p.Asp80Asp	synonymous	Exon 5 of 27	ENSP00000262811.4	O60307
MAST3	ENST00000697701.1		c.306C>T	p.Asp102Asp	synonymous	Exon 5 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes

AF:

0.000250

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000259

AC:

AN:

247130

AF XY:

0.000276

show subpopulations

Gnomad AFR exome

AF:

0.000262

Gnomad AMR exome

AF:

0.000350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000357

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.000203

AC:

296

AN:

1460664

Hom.:

Cov.:

AF XY:

0.000204

AC XY:

148

AN XY:

726482

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33472

American (AMR)

AF:

0.000382

AC:

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26098

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000116

AC:

AN:

85940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000225

AC:

250

AN:

1111442

Other (OTH)

AF:

0.000133

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000243

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41564

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000164

Hom.:

Bravo

AF:

0.000246

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000417

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MAST3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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