19-18144549-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393504.1(MAST3):​c.2668G>C​(p.Gly890Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G890S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MAST3 NM_001393504.1 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14962855).

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>C	p.Gly890Arg	missense	Exon 23 of 28	NP_001380433.1
	MAST3	NM_001393501.1		c.2692G>C	p.Gly898Arg	missense	Exon 24 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.2671G>C	p.Gly891Arg	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>C	p.Gly890Arg	missense	Exon 23 of 28	ENSP00000509890.1
	MAST3	ENST00000262811.10	TSL:1	c.2581G>C	p.Gly861Arg	missense	Exon 22 of 27	ENSP00000262811.4
	MAST3	ENST00000697701.1		c.2647G>C	p.Gly883Arg	missense	Exon 22 of 27	ENSP00000513408.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457716 Hom.: 0 Cov.: 71 AF XY: 0.00000138 AC XY: 1 AN XY: 725262

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44380

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51014

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111066

Other (OTH) AF: 0.00 AC: 0 AN: 60234

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.90
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	2.0	M
PhyloP100		2.3
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.039
Sift	Benign	0.25	T
Sift4G	Benign	0.47	T
Polyphen		0.021	B
Vest4		0.18
MutPred		0.29		Gain of MoRF binding (P = 0.025)
MVP		0.51
MPC		1.1
ClinPred		0.12	T
GERP RS		2.3
Varity_R		0.065
gMVP		0.41
Mutation Taster		=97/3	polymorphism

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: rs8108738; hg19: chr19-18255359;