19-18144549-G-A

Variant names:

• chr19-18144549-G-A
• rs8108738
• NM_001393504.1:c.2668G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001393504.1(MAST3):​c.2668G>A​(p.Gly890Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,609,598 control chromosomes in the GnomAD database, including 227,209 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18175 hom., cov: 33)
  • Exomes 𝑓: 0.53 (209034 hom.)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.25
• Publications: 43 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.170261E-6).
• BP6: Variant 19-18144549-G-A is Benign according to our data. Variant chr19-18144549-G-A is described in ClinVar as Benign. ClinVar VariationId is 1526372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.669 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	NM_001393504.1	MANE Select	c.2668G>A	p.Gly890Ser	missense	Exon 23 of 28	NP_001380433.1
	MAST3	NM_001393501.1		c.2692G>A	p.Gly898Ser	missense	Exon 24 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.2671G>A	p.Gly891Ser	missense	Exon 23 of 28	NP_001380431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.2668G>A	p.Gly890Ser	missense	Exon 23 of 28	ENSP00000509890.1
	MAST3	ENST00000262811.10	TSL:1	c.2581G>A	p.Gly861Ser	missense	Exon 22 of 27	ENSP00000262811.4
	MAST3	ENST00000697701.1		c.2647G>A	p.Gly883Ser	missense	Exon 22 of 27	ENSP00000513408.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 73011 AN: 151998 Hom.: 18177 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.471

GnomAD2 exomes AF: 0.535 AC: 129059 AN: 241430 AF XY: 0.540

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.446

Gnomad EAS exome AF: 0.691

Gnomad FIN exome AF: 0.505

Gnomad NFE exome AF: 0.525

Gnomad OTH exome AF: 0.516

GnomAD4 exome AF: 0.532 AC: 775892 AN: 1457482 Hom.: 209034 Cov.: 71 AF XY: 0.535 AC XY: 387975 AN XY: 725148

African (AFR) AF: 0.334 AC: 11184 AN: 33438

American (AMR) AF: 0.512 AC: 22739 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11811 AN: 26002

East Asian (EAS) AF: 0.701 AC: 27802 AN: 39672

South Asian (SAS) AF: 0.640 AC: 55080 AN: 86128

European-Finnish (FIN) AF: 0.503 AC: 25587 AN: 50918

Middle Eastern (MID) AF: 0.437 AC: 2508 AN: 5744

European-Non Finnish (NFE) AF: 0.529 AC: 587856 AN: 1110986

Other (OTH) AF: 0.520 AC: 31325 AN: 60224

GnomAD4 genome AF: 0.480 AC: 73027 AN: 152116 Hom.: 18175 Cov.: 33 AF XY: 0.481 AC XY: 35736 AN XY: 74364

African (AFR) AF: 0.348 AC: 14455 AN: 41512

American (AMR) AF: 0.494 AC: 7551 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1653 AN: 3472

East Asian (EAS) AF: 0.688 AC: 3553 AN: 5166

South Asian (SAS) AF: 0.648 AC: 3123 AN: 4820

European-Finnish (FIN) AF: 0.503 AC: 5328 AN: 10584

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

European-Non Finnish (NFE) AF: 0.523 AC: 35559 AN: 67968

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.512 Hom.: 87773

Bravo AF: 0.470

TwinsUK AF: 0.529 AC: 1960

ALSPAC AF: 0.519 AC: 1999

ESP6500AA AF: 0.342 AC: 1317

ESP6500EA AF: 0.521 AC: 4297

ExAC AF: 0.534 AC: 64279

Asia WGS AF: 0.635 AC: 2209 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 22, 2022

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0000082	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.15
Sift	Benign	0.34	T
Sift4G	Benign	0.67	T
Polyphen		0.0020	B
Vest4		0.020
MPC		0.74
ClinPred		0.0047	T
GERP RS		2.3
Varity_R		0.059
gMVP		0.27
Mutation Taster		=99/1	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: rs8108738; hg19: chr19-18255359; COSMIC: COSV53224529; COSMIC: COSV53224529;