1-45997731-T-G

Position:

• chr1-45997731-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015112.3(MAST2):​c.600T>G​(p.Ser200Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST2	NM_015112.3	c.600T>G	p.Ser200Arg	missense_variant	6/29	ENST00000361297.7	NP_055927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST2	ENST00000361297.7	c.600T>G	p.Ser200Arg	missense_variant	6/29	1	NM_015112.3	ENSP00000354671
MAST2	ENST00000674079.1	c.150T>G	p.Ser50Arg	missense_variant	3/27			ENSP00000501318	P1
MAST2	ENST00000372008.6	c.255T>G	p.Ser85Arg	missense_variant	4/20	5		ENSP00000361078
MAST2	ENST00000482881.1	n.100T>G		non_coding_transcript_exon_variant	2/6	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.600T>G (p.S200R) alteration is located in exon 6 (coding exon 6) of the MAST2 gene. This alteration results from a T to G substitution at nucleotide position 600, causing the serine (S) at amino acid position 200 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;T
Polyphen		1.0	D;.
Vest4		0.73
MutPred		0.54		Loss of phosphorylation at S200 (P = 0.0435);.;
MVP		0.86
MPC		0.89
ClinPred		0.99	D
GERP RS		5.7
Varity_R		0.83
gMVP		0.73

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-46463403;