5-67090209-G-T

Position:

• chr5-67090209-G-T

Variant summary

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

The NM_001164664.2(MAST4):​c.811G>T​(p.Ala271Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MAST4 NM_001164664.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.26

Genes affected

MAST4 (HGNC:19037): (microtubule associated serine/threonine kinase family member 4) This gene encodes a member of the microtubule-associated serine/threonine protein kinases. The proteins in this family contain a domain that gives the kinase the ability to determine its own scaffold to control the effects of their kinase activities. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014]

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
MAST4	NM_001164664.2	c.811G>T	p.Ala271Ser	missense_variant	6/29	ENST00000403625.7	NP_001158136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST4	ENST00000403625.7	c.811G>T	p.Ala271Ser	missense_variant	6/29	5	NM_001164664.2	ENSP00000385727.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

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

Nov 30, 2024

The c.244G>T (p.A82S) alteration is located in exon 5 (coding exon 5) of the MAST4 gene. This alteration results from a G to T substitution at nucleotide position 244, causing the alanine (A) at amino acid position 82 to be replaced by a serine (S). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T;.;.;.;.;T
Eigen	Uncertain	0.64
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.53	D;D;D;D;D;D
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.4	M;.;.;.;.;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.5	N;D;N;N;N;D
REVEL	Benign	0.16
Sift	Benign	0.035	D;T;D;D;D;T
Sift4G	Uncertain	0.038	D;T;T;T;T;T
Polyphen		1.0	D;B;P;.;D;.
Vest4		0.37
MutPred		0.51		Gain of phosphorylation at A271 (P = 0.0205);.;.;.;.;.;
MVP		0.77
MPC		0.80
ClinPred		0.94	D
GERP RS		5.8
Varity_R		0.16
gMVP		0.37

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

LitVar

Other links and lift over

dbSNP: rs1763675927; hg19: chr5-66386037;