19-18123611-G-A

Variant names:

• chr19-18123611-G-A
• rs971458049
• NM_001393504.1:c.589G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001393504.1(MAST3):​c.589G>A​(p.Glu197Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.86

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.744

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAST3	NM_001393504.1	c.589G>A	p.Glu197Lys	missense_variant	Exon 8 of 28	ENST00000687212.1	NP_001380433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAST3	ENST00000687212.1	c.589G>A	p.Glu197Lys	missense_variant	Exon 8 of 28		NM_001393504.1	ENSP00000509890.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 02, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.74	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.034	D
Polyphen		0.51	P
Vest4		0.56
MutPred		0.78		Gain of MoRF binding (P = 0.0021);
MVP		0.78
MPC		1.5
ClinPred		0.97	D
GERP RS		4.7
Varity_R		0.37
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs971458049; hg19: chr19-18234421; COSMIC: COSV53220818;