5-67100500-C-G

Position:

• chr5-67100500-C-G

Variant summary

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

The NM_001164664.2(MAST4):​c.978C>G​(p.His326Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,134 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MAST4 NM_001164664.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.47

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	UniProt
MAST4	NM_001164664.2	c.978C>G	p.His326Gln	missense_variant	8/29	ENST00000403625.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAST4	ENST00000403625.7	c.978C>G	p.His326Gln	missense_variant	8/29	5	NM_001164664.2	A2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

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 Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152134 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74308

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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

Feb 16, 2023

The c.411C>G (p.H137Q) alteration is located in exon 7 (coding exon 7) of the MAST4 gene. This alteration results from a C to G substitution at nucleotide position 411, causing the histidine (H) at amino acid position 137 to be replaced by a glutamine (Q). 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	0.87
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.055	.;.;.;.;.;T
Eigen	Benign	0.14
Eigen_PC	Benign	0.099
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.63	D;D;D;D;D;D
MetaSVM	Benign	-0.88	T
MutationTaster	Benign	0.94	N;N;N;N;N;N
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-7.4	D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Benign	0.051	T;T;D;D;D;T
Sift4G	Benign	0.14	T;T;T;T;T;T
Polyphen		0.62, 0.94, 1.0	.;P;P;.;D;.
Vest4		0.79
MVP		0.56
MPC		1.2
ClinPred		0.88	D
GERP RS		3.4
Varity_R		0.48
gMVP		0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs1764912143; hg19: chr5-66396328;