NM_015112.3:c.146C>G

Variant names:

• chr1-45804041-C-G
• rs1644064745
• NM_015112.3:c.146C>G

Variant summary

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

The NM_015112.3(MAST2):​c.146C>G​(p.Thr49Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.590
• Publications: 0 publications found

Genes affected

MAST2 (HGNC:19035): (microtubule associated serine/threonine kinase 2) Enables phosphatase binding activity. Predicted to be involved in several processes, including peptidyl-serine phosphorylation; regulation of interleukin-12 production; and spermatid differentiation. Predicted to be located in cytoplasm and plasma membrane. Predicted to be active in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MAST2 Gene-Disease associations (from GenCC):

• thrombotic disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

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=0.11701578).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015112.3. 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
	MAST2	NM_015112.3	MANE Select	c.146C>G	p.Thr49Arg	missense	Exon 1 of 29	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.146C>G	p.Thr49Arg	missense	Exon 1 of 30	NP_001311249.1
	MAST2	NM_001319245.2		c.146C>G	p.Thr49Arg	missense	Exon 1 of 29	NP_001306174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	ENST00000361297.7	TSL:1 MANE Select	c.146C>G	p.Thr49Arg	missense	Exon 1 of 29	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.146C>G	p.Thr49Arg	missense	Exon 1 of 30	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.146C>G	p.Thr49Arg	missense	Exon 1 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000183 AC: 2 AN: 1095766 Hom.: 0 Cov.: 22 AF XY: 0.00000191 AC XY: 1 AN XY: 523046

African (AFR) AF: 0.00 AC: 0 AN: 22250

American (AMR) AF: 0.00 AC: 0 AN: 8020

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14224

East Asian (EAS) AF: 0.00 AC: 0 AN: 25474

South Asian (SAS) AF: 0.0000322 AC: 1 AN: 31080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2884

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 913876

Other (OTH) AF: 0.0000230 AC: 1 AN: 43552

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.0064	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.46	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.59
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.039
Sift	Uncertain	0.015	D
Sift4G	Benign	0.53	T
Polyphen		0.069	B
Vest4		0.17
MutPred		0.14		Loss of phosphorylation at T49 (P = 0.0119)
MVP		0.64
MPC		0.34
ClinPred		0.23	T
GERP RS		1.8
PromoterAI		-0.078	Neutral
Varity_R		0.076
gMVP		0.16
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: rs1644064745; hg19: chr1-46269713;