19-18146940-C-T

Variant names:

• chr19-18146940-C-T
• rs2072490
• NM_001393504.1:c.3222C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001393504.1(MAST3):​c.3222C>T​(p.Gly1074Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,557,264 control chromosomes in the GnomAD database, including 219,292 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 0.49 (18449 hom., cov: 30)
  • Exomes 𝑓: 0.53 (200843 hom.)
• Consequence: MAST3 NM_001393504.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• 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-AS1 (HGNC:55276): (MAST3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAST3	NM_001393504.1	c.3222C>T	p.Gly1074Gly	synonymous_variant	Exon 26 of 28	ENST00000687212.1	NP_001380433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAST3	ENST00000687212.1	c.3222C>T	p.Gly1074Gly	synonymous_variant	Exon 26 of 28		NM_001393504.1	ENSP00000509890.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73782 AN: 151650 Hom.: 18450 Cov.: 30

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.477

GnomAD2 exomes AF: 0.532 AC: 87121 AN: 163656 AF XY: 0.539

Gnomad AFR exome AF: 0.361

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.685

Gnomad FIN exome AF: 0.501

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.510

GnomAD4 exome AF: 0.532 AC: 747298 AN: 1405492 Hom.: 200843 Cov.: 50 AF XY: 0.534 AC XY: 370625 AN XY: 693920

African (AFR) AF: 0.361 AC: 11522 AN: 31928

American (AMR) AF: 0.511 AC: 18552 AN: 36280

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11471 AN: 25280

East Asian (EAS) AF: 0.702 AC: 25538 AN: 36372

South Asian (SAS) AF: 0.636 AC: 50633 AN: 79562

European-Finnish (FIN) AF: 0.502 AC: 24857 AN: 49556

Middle Eastern (MID) AF: 0.434 AC: 2455 AN: 5652

European-Non Finnish (NFE) AF: 0.528 AC: 572015 AN: 1082584

Other (OTH) AF: 0.519 AC: 30255 AN: 58278

GnomAD4 genome AF: 0.486 AC: 73797 AN: 151772 Hom.: 18449 Cov.: 30 AF XY: 0.486 AC XY: 36041 AN XY: 74148

African (AFR) AF: 0.373 AC: 15421 AN: 41392

American (AMR) AF: 0.495 AC: 7549 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3468

East Asian (EAS) AF: 0.688 AC: 3531 AN: 5132

South Asian (SAS) AF: 0.646 AC: 3107 AN: 4806

European-Finnish (FIN) AF: 0.501 AC: 5273 AN: 10516

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.522 AC: 35452 AN: 67886

Other (OTH) AF: 0.481 AC: 1014 AN: 2108

Alfa AF: 0.516 Hom.: 63164

Bravo AF: 0.477

Asia WGS AF: 0.634 AC: 2202 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		-2.5
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.40		Position offset: -6

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

Other links and lift over

dbSNP: rs2072490; hg19: chr19-18257750; COSMIC: COSV53227454; COSMIC: COSV53227454;