19-18137336-T-C

Position:

• chr19-18137336-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001393504.1(MAST3):​c.2070T>C​(p.Ala690Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,613,740 control chromosomes in the GnomAD database, including 709,440 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 0.94 (67177 hom., cov: 31)
  • Exomes 𝑓: 0.94 (642263 hom.)
• Consequence: MAST3 NM_001393504.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.99

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-5.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST3	NM_001393504.1	c.2070T>C	p.Ala690Ala	synonymous_variant	19/28	ENST00000687212.1	NP_001380433.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST3	ENST00000687212.1	c.2070T>C	p.Ala690Ala	synonymous_variant	19/28		NM_001393504.1	ENSP00000509890.1

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142875 AN: 152122 Hom.: 67120 Cov.: 31

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.964

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.935

Gnomad OTH AF: 0.935

GnomAD3 exomes AF: 0.940 AC: 234101 AN: 249048 Hom.: 110088 AF XY: 0.938 AC XY: 126770 AN XY: 135128

Gnomad AFR exome AF: 0.940

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.929

Gnomad EAS exome AF: 0.966

Gnomad SAS exome AF: 0.928

Gnomad FIN exome AF: 0.948

Gnomad NFE exome AF: 0.935

Gnomad OTH exome AF: 0.920

GnomAD4 exome AF: 0.937 AC: 1369906 AN: 1461500 Hom.: 642263 Cov.: 51 AF XY: 0.937 AC XY: 680935 AN XY: 727036

Gnomad4 AFR exome AF: 0.938

Gnomad4 AMR exome AF: 0.951

Gnomad4 ASJ exome AF: 0.929

Gnomad4 EAS exome AF: 0.961

Gnomad4 SAS exome AF: 0.927

Gnomad4 FIN exome AF: 0.947

Gnomad4 NFE exome AF: 0.937

Gnomad4 OTH exome AF: 0.937

GnomAD4 genome AF: 0.939 AC: 142991 AN: 152240 Hom.: 67177 Cov.: 31 AF XY: 0.940 AC XY: 69921 AN XY: 74422

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.931

Gnomad4 EAS AF: 0.964

Gnomad4 SAS AF: 0.927

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.935

Gnomad4 OTH AF: 0.937

Alfa AF: 0.935 Hom.: 79094

Bravo AF: 0.939

Asia WGS AF: 0.945 AC: 3286 AN: 3478

EpiCase AF: 0.933

EpiControl AF: 0.931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.82
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs541225; hg19: chr19-18248146;