chr19-18137336-T-C

Variant names:

• chr19-18137336-T-C
• rs541225
• NM_001393504.1:c.2070T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001393504.1(MAST3):​c.2070T>C​(p.Ala690Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,613,740 control chromosomes in the GnomAD database, including 709,440 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.94 (67177 hom., cov: 31)
  • Exomes 𝑓: 0.94 (642263 hom.)
• Consequence: MAST3 NM_001393504.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.99
• Publications: 19 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-5.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	NM_001393504.1	MANE Select	c.2070T>C	p.Ala690Ala	synonymous	Exon 19 of 28	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.2094T>C	p.Ala698Ala	synonymous	Exon 20 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.2073T>C	p.Ala691Ala	synonymous	Exon 19 of 28	NP_001380431.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.2070T>C	p.Ala690Ala	synonymous	Exon 19 of 28	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.1983T>C	p.Ala661Ala	synonymous	Exon 18 of 27	ENSP00000262811.4	O60307
	MAST3	ENST00000697701.1		c.2049T>C	p.Ala683Ala	synonymous	Exon 18 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142875 AN: 152122 Hom.: 67120 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.935

GnomAD2 exomes AF: 0.940 AC: 234101 AN: 249048 AF XY: 0.938

Gnomad AFR exome AF: 0.940

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 0.966

Gnomad FIN exome AF: 0.948

Gnomad NFE exome AF: 0.935

Gnomad OTH exome AF: 0.920

GnomAD4 exome AF: 0.937 AC: 1369906 AN: 1461500 Hom.: 642263 Cov.: 51 AF XY: 0.937 AC XY: 680935 AN XY: 727036

African (AFR) AF: 0.938 AC: 31404 AN: 33478

American (AMR) AF: 0.951 AC: 42517 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 24270 AN: 26122

East Asian (EAS) AF: 0.961 AC: 38132 AN: 39694

South Asian (SAS) AF: 0.927 AC: 79936 AN: 86254

European-Finnish (FIN) AF: 0.947 AC: 50539 AN: 53372

Middle Eastern (MID) AF: 0.882 AC: 5087 AN: 5768

European-Non Finnish (NFE) AF: 0.937 AC: 1041469 AN: 1111736

Other (OTH) AF: 0.937 AC: 56552 AN: 60364

GnomAD4 genome AF: 0.939 AC: 142991 AN: 152240 Hom.: 67177 Cov.: 31 AF XY: 0.940 AC XY: 69921 AN XY: 74422

African (AFR) AF: 0.941 AC: 39113 AN: 41558

American (AMR) AF: 0.941 AC: 14393 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3230 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4979 AN: 5164

South Asian (SAS) AF: 0.927 AC: 4477 AN: 4830

European-Finnish (FIN) AF: 0.951 AC: 10098 AN: 10614

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.935 AC: 63569 AN: 67994

Other (OTH) AF: 0.937 AC: 1981 AN: 2114

Alfa AF: 0.936 Hom.: 110169

Bravo AF: 0.939

Asia WGS AF: 0.945 AC: 3286 AN: 3478

EpiCase AF: 0.933

EpiControl AF: 0.931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.48
PhyloP100		-6.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs541225; hg19: chr19-18248146; COSMIC: COSV108071407; COSMIC: COSV108071407;