rs273504

Variant names:

• chr19-18104437-A-G
• rs273504
• NM_001393504.1:c.40-3150A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393504.1(MAST3):​c.40-3150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 151,330 control chromosomes in the GnomAD database, including 16,279 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16279 hom., cov: 28)
• Consequence: MAST3 NM_001393504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

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.40-3150A>G		intron	N/A	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.40-3150A>G		intron	N/A	NP_001380430.1
	MAST3	NM_001393502.1		c.40-3150A>G		intron	N/A	NP_001380431.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.40-3150A>G		intron	N/A	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.40-3150A>G		intron	N/A	ENSP00000262811.4	O60307
	MAST3	ENST00000893417.1		c.40-3150A>G		intron	N/A	ENSP00000563476.1

Frequencies

GnomAD3 genomes AF: 0.458 AC: 69221 AN: 151212 Hom.: 16246 Cov.: 28

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.472

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.458 AC: 69313 AN: 151330 Hom.: 16279 Cov.: 28 AF XY: 0.459 AC XY: 33901 AN XY: 73894

African (AFR) AF: 0.540 AC: 22253 AN: 41200

American (AMR) AF: 0.465 AC: 7041 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 1497 AN: 3462

East Asian (EAS) AF: 0.331 AC: 1692 AN: 5112

South Asian (SAS) AF: 0.259 AC: 1242 AN: 4794

European-Finnish (FIN) AF: 0.491 AC: 5156 AN: 10498

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29088 AN: 67804

Other (OTH) AF: 0.468 AC: 984 AN: 2102

Alfa AF: 0.449 Hom.: 19729

Bravo AF: 0.466

Asia WGS AF: 0.333 AC: 1162 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.55
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs273504; hg19: chr19-18215247;