chr5-67166241-A-G

Variant names:

• chr5-67166241-A-G
• rs4699896
• NM_001164664.2:c.7062A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP6_Very_Strong BP7 BA1

The NM_001164664.2(MAST4):​c.7062A>G​(p.Thr2354Thr) 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. 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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -17 ACMG points.

• BP6: Variant 5-67166241-A-G is Benign according to our data. Variant chr5-67166241-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164664.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST4	NM_001164664.2	MANE Select	c.7062A>G	p.Thr2354Thr	synonymous	Exon 29 of 29	NP_001158136.1
	MAST4	NM_001393524.1		c.7071A>G	p.Thr2357Thr	synonymous	Exon 30 of 30	NP_001380453.1
	MAST4	NM_001393525.1		c.6861A>G	p.Thr2287Thr	synonymous	Exon 28 of 28	NP_001380454.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST4	ENST00000403625.7	TSL:5 MANE Select	c.7062A>G	p.Thr2354Thr	synonymous	Exon 29 of 29	ENSP00000385727.1
	MAST4	ENST00000403666.5	TSL:1	c.6495A>G	p.Thr2165Thr	synonymous	Exon 28 of 28	ENSP00000384313.1
	MAST4	ENST00000443808.1	TSL:1	c.4230A>G	p.Thr1410Thr	synonymous	Exon 8 of 8	ENSP00000400551.1

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

GnomAD2 exomes AF: 0.0918 AC: 14548 AN: 158510 AF XY: 0.0820

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 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

African (AFR) AF: 0.350 AC: 10992 AN: 31434

American (AMR) AF: 0.229 AC: 8175 AN: 35736

Ashkenazi Jewish (ASJ) AF: 0.0273 AC: 688 AN: 25186

East Asian (EAS) AF: 0.208 AC: 7454 AN: 35782

South Asian (SAS) AF: 0.0806 AC: 6393 AN: 79330

European-Finnish (FIN) AF: 0.0359 AC: 1773 AN: 49386

Middle Eastern (MID) AF: 0.0388 AC: 221 AN: 5700

European-Non Finnish (NFE) AF: 0.0104 AC: 11237 AN: 1079420

Other (OTH) AF: 0.0611 AC: 3546 AN: 58026

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

African (AFR) AF: 0.345 AC: 14246 AN: 41240

American (AMR) AF: 0.173 AC: 2637 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5180

South Asian (SAS) AF: 0.0931 AC: 450 AN: 4832

European-Finnish (FIN) AF: 0.0358 AC: 380 AN: 10624

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0118 AC: 803 AN: 68028

Other (OTH) AF: 0.112 AC: 236 AN: 2114

Alfa AF: 0.0485 Hom.: 2155

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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