chr1-45803995-C-T

Variant names:

• chr1-45803995-C-T
• rs1229800479
• NM_015112.3:c.100C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015112.3(MAST2):​c.100C>T​(p.Pro34Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000604 in 1,159,342 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0770
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06172034).

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.100C>T	p.Pro34Ser	missense	Exon 1 of 29	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.100C>T	p.Pro34Ser	missense	Exon 1 of 30	NP_001311249.1
	MAST2	NM_001319245.2		c.100C>T	p.Pro34Ser	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.100C>T	p.Pro34Ser	missense	Exon 1 of 29	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.100C>T	p.Pro34Ser	missense	Exon 1 of 30	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.100C>T	p.Pro34Ser	missense	Exon 1 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151908 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000496 AC: 5 AN: 1007326 Hom.: 0 Cov.: 14 AF XY: 0.00000412 AC XY: 2 AN XY: 485474

African (AFR) AF: 0.00 AC: 0 AN: 20504

American (AMR) AF: 0.00 AC: 0 AN: 8306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14400

East Asian (EAS) AF: 0.000154 AC: 4 AN: 26008

South Asian (SAS) AF: 0.00 AC: 0 AN: 33054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2802

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 824804

Other (OTH) AF: 0.0000242 AC: 1 AN: 41330

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152016 Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1 AN XY: 74298

African (AFR) AF: 0.00 AC: 0 AN: 41508

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000389 AC: 2 AN: 5138

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

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	0.074
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.38	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.077
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.16	N
REVEL	Benign	0.028
Sift	Benign	0.74	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.22		Gain of phosphorylation at P34 (P = 0.0013)
MVP		0.30
MPC		0.23
ClinPred		0.12	T
GERP RS		-1.7
PromoterAI		0.012	Neutral
Varity_R		0.025
gMVP		0.15
Mutation Taster		=98/2	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: rs1229800479; hg19: chr1-46269667;