chr19-18123631-C-G

Variant names:

• chr19-18123631-C-G
• rs740691
• NM_001393504.1:c.609C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001393504.1(MAST3):​c.609C>G​(p.His203Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 24 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	NM_001393504.1	MANE Select	c.609C>G	p.His203Gln	missense	Exon 8 of 28	NP_001380433.1
	MAST3	NM_001393501.1		c.633C>G	p.His211Gln	missense	Exon 9 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.612C>G	p.His204Gln	missense	Exon 8 of 28	NP_001380431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.609C>G	p.His203Gln	missense	Exon 8 of 28	ENSP00000509890.1
	MAST3	ENST00000262811.10	TSL:1	c.522C>G	p.His174Gln	missense	Exon 7 of 27	ENSP00000262811.4
	MAST3	ENST00000697701.1		c.588C>G	p.His196Gln	missense	Exon 7 of 27	ENSP00000513408.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.063	N
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.33	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		-2.0
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.32
Sift	Benign	0.053	T
Sift4G	Uncertain	0.058	T
Polyphen		0.99	D
Vest4		0.50
MutPred		0.65		Gain of disorder (P = 0.0561)
MVP		0.51
MPC		2.1
ClinPred		0.68	D
GERP RS		-9.4
Varity_R		0.53
gMVP		0.62
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.20		Position offset: 0

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

Other links and lift over

dbSNP: rs740691; hg19: chr19-18234441;