rs740691

Positions:

• chr19-18123631-C-G
• chr19-18123631-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

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

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MAST3. . Gene score misZ 4.1363 (greater than the threshold 3.09). Trascript score misZ 3.5232 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy 108.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST3	NM_001393504.1	c.609C>G	p.His203Gln	missense_variant	8/28	ENST00000687212.1	NP_001380433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST3	ENST00000687212.1	c.609C>G	p.His203Gln	missense_variant	8/28		NM_001393504.1	ENSP00000509890.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs740691; hg19: chr19-18234441;