rs2270623

Variant names:

• chr19-18134702-C-G
• rs2270623
• NM_001393504.1:c.1695C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-18134702-C-G
• chr19-18134702-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393504.1(MAST3):​c.1695C>G​(p.Ile565Met) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I565V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 23 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095157415).

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.1695C>G	p.Ile565Met	missense	Exon 16 of 28	NP_001380433.1
	MAST3	NM_001393501.1		c.1719C>G	p.Ile573Met	missense	Exon 17 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.1698C>G	p.Ile566Met	missense	Exon 16 of 28	NP_001380431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.1695C>G	p.Ile565Met	missense	Exon 16 of 28	ENSP00000509890.1
	MAST3	ENST00000262811.10	TSL:1	c.1608C>G	p.Ile536Met	missense	Exon 15 of 27	ENSP00000262811.4
	MAST3	ENST00000697701.1		c.1674C>G	p.Ile558Met	missense	Exon 15 of 27	ENSP00000513408.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 29300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.5
DANN	Benign	0.58
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.27	N
PhyloP100		0.73
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.081
Sift	Benign	0.13	T
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.045
MutPred		0.39		Gain of disorder (P = 0.0746)
MVP		0.31
MPC		0.96
ClinPred		0.056	T
GERP RS		-0.32
Varity_R		0.062
gMVP		0.70
Mutation Taster		=93/7	polymorphism

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: rs2270623; hg19: chr19-18245512;