19-18123631-C-T

Variant names:

• chr19-18123631-C-T
• rs740691
• NM_001393504.1:c.609C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001393504.1(MAST3):​c.609C>T​(p.His203His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 1,585,874 control chromosomes in the GnomAD database, including 228,441 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 0.52 (20396 hom., cov: 33)
  • Exomes 𝑓: 0.54 (208045 hom.)
• Consequence: MAST3 NM_001393504.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 24 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP7: Synonymous conserved (PhyloP=-2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 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.609C>T	p.His203His	synonymous	Exon 8 of 28	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.633C>T	p.His211His	synonymous	Exon 9 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.612C>T	p.His204His	synonymous	Exon 8 of 28	NP_001380431.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.609C>T	p.His203His	synonymous	Exon 8 of 28	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.522C>T	p.His174His	synonymous	Exon 7 of 27	ENSP00000262811.4	O60307
	MAST3	ENST00000697701.1		c.588C>T	p.His196His	synonymous	Exon 7 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78340 AN: 151958 Hom.: 20395 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.649

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.525 AC: 114027 AN: 217052 AF XY: 0.528

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.497

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.670

Gnomad FIN exome AF: 0.487

Gnomad NFE exome AF: 0.511

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.537 AC: 769492 AN: 1433798 Hom.: 208045 Cov.: 50 AF XY: 0.538 AC XY: 382745 AN XY: 710964

African (AFR) AF: 0.448 AC: 14684 AN: 32812

American (AMR) AF: 0.498 AC: 19970 AN: 40126

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 11594 AN: 24802

East Asian (EAS) AF: 0.678 AC: 26571 AN: 39212

South Asian (SAS) AF: 0.633 AC: 51512 AN: 81390

European-Finnish (FIN) AF: 0.496 AC: 25775 AN: 52016

Middle Eastern (MID) AF: 0.441 AC: 2512 AN: 5694

European-Non Finnish (NFE) AF: 0.533 AC: 585569 AN: 1098512

Other (OTH) AF: 0.528 AC: 31305 AN: 59234

GnomAD4 genome AF: 0.515 AC: 78364 AN: 152076 Hom.: 20396 Cov.: 33 AF XY: 0.514 AC XY: 38211 AN XY: 74334

African (AFR) AF: 0.464 AC: 19230 AN: 41488

American (AMR) AF: 0.505 AC: 7729 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1720 AN: 3470

East Asian (EAS) AF: 0.675 AC: 3477 AN: 5152

South Asian (SAS) AF: 0.649 AC: 3121 AN: 4808

European-Finnish (FIN) AF: 0.499 AC: 5275 AN: 10576

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35942 AN: 67966

Other (OTH) AF: 0.502 AC: 1060 AN: 2112

Alfa AF: 0.518 Hom.: 58224

Bravo AF: 0.510

Asia WGS AF: 0.625 AC: 2173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.60
DANN	Benign	0.63
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs740691; hg19: chr19-18234441; COSMIC: COSV53224268;