chr19-18145090-G-A

Variant names:

• chr19-18145090-G-A
• rs752684786
• NM_001393504.1:c.2900G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001393504.1(MAST3):​c.2900G>A​(p.Arg967Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.90
• 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-AS1 (HGNC:55276): (MAST3 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.2900G>A	p.Arg967Gln	missense	Exon 24 of 28	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.2924G>A	p.Arg975Gln	missense	Exon 25 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.2903G>A	p.Arg968Gln	missense	Exon 24 of 28	NP_001380431.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.2900G>A	p.Arg967Gln	missense	Exon 24 of 28	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.2813G>A	p.Arg938Gln	missense	Exon 23 of 27	ENSP00000262811.4	O60307
	MAST3	ENST00000697701.1		c.2879G>A	p.Arg960Gln	missense	Exon 23 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151920 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248890 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461366 Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4 AN XY: 726996

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111864

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151920 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74168

African (AFR) AF: 0.00 AC: 0 AN: 41334

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67994

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000827 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	34
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Uncertain	0.24	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	1.9	L
PhyloP100		9.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.077	T
Polyphen		1.0	D
Vest4		0.67
MutPred		0.15		Loss of glycosylation at S937 (P = 0.0875)
MVP		0.75
MPC		1.9
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.65
gMVP		0.42
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: 3

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

Other links and lift over

dbSNP: rs752684786; hg19: chr19-18255900;