rs4699896

Positions:

• chr5-67166241-A-G
• chr5-67166241-A-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001164664.2(MAST4):​c.7062A>G​(p.Thr2354=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0454 in 1,551,978 control chromosomes in the GnomAD database, including 7,433 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2898 hom., cov: 32)
  • Exomes 𝑓: 0.036 (4535 hom.)
• Consequence: MAST4 NM_001164664.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.534

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-67166241-A-G is Benign according to our data. Variant chr5-67166241-A-G is described in ClinVar as [Benign]. Clinvar id is 1304156.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.534 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST4	NM_001164664.2	c.7062A>G	p.Thr2354=	synonymous_variant	29/29	ENST00000403625.7	NP_001158136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST4	ENST00000403625.7	c.7062A>G	p.Thr2354=	synonymous_variant	29/29	5	NM_001164664.2	ENSP00000385727	A2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19888 AN: 151862 Hom.: 2865 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.109

GnomAD3 exomes AF: 0.0918 AC: 14548 AN: 158510 Hom.: 1621 AF XY: 0.0820 AC XY: 6865 AN XY: 83764

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.0267

Gnomad EAS exome AF: 0.194

Gnomad SAS exome AF: 0.0814

Gnomad FIN exome AF: 0.0385

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.0707

GnomAD4 exome AF: 0.0361 AC: 50479 AN: 1400000 Hom.: 4535 Cov.: 36 AF XY: 0.0357 AC XY: 24643 AN XY: 690598

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.229

Gnomad4 ASJ exome AF: 0.0273

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.0806

Gnomad4 FIN exome AF: 0.0359

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0611

GnomAD4 genome AF: 0.131 AC: 19982 AN: 151978 Hom.: 2898 Cov.: 32 AF XY: 0.133 AC XY: 9854 AN XY: 74336

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.0931

Gnomad4 FIN AF: 0.0358

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0452 Hom.: 899

Bravo AF: 0.155

Asia WGS AF: 0.178 AC: 617 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.5
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs4699896; hg19: chr5-66462069; COSMIC: COSV55116077;