19-18122691-G-C

Variant names:

• chr19-18122691-G-C
• NM_001393504.1:c.339G>C
• MAST3 p.Trp113Cys

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001393504.1(MAST3):​c.339G>C​(p.Trp113Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.44
• Publications: 0 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)

ENSG00000297168 (HGNC:):

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.964

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.339G>C	p.Trp113Cys	missense	Exon 6 of 28	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.363G>C	p.Trp121Cys	missense	Exon 7 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.342G>C	p.Trp114Cys	missense	Exon 6 of 28	NP_001380431.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.339G>C	p.Trp113Cys	missense	Exon 6 of 28	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.252G>C	p.Trp84Cys	missense	Exon 5 of 27	ENSP00000262811.4	O60307
	MAST3	ENST00000697701.1		c.318G>C	p.Trp106Cys	missense	Exon 5 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	33
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Pathogenic	0.38	D
MetaRNN	Pathogenic	0.96	D
MetaSVM	Uncertain	-0.0064	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		9.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-12	D
REVEL	Pathogenic	0.71
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Varity_R		0.73
gMVP		0.91
Mutation Taster		=36/64	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-18233501;