19-18137336-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001393504.1(MAST3):​c.2070T>A​(p.Ala690Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-5.99 with no splicing effect.

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>A	p.Ala690Ala	synonymous	Exon 19 of 28	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.2094T>A	p.Ala698Ala	synonymous	Exon 20 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.2073T>A	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>A	p.Ala690Ala	synonymous	Exon 19 of 28	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.1983T>A	p.Ala661Ala	synonymous	Exon 18 of 27	ENSP00000262811.4	O60307
	MAST3	ENST00000697701.1		c.2049T>A	p.Ala683Ala	synonymous	Exon 18 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 51

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.73
DANN	Benign	0.60
PhyloP100		-6.0

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;