rs39861

chr5-66856430-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164664.2(MAST4):c.643-43521A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,132 control chromosomes in the GnomAD database, including 5,020 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5020 hom., cov: 33)
• Consequence: MAST4 NM_001164664.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAST4	NM_001164664.2	c.643-43521A>G		intron_variant		ENST00000403625.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAST4	ENST00000403625.7	c.643-43521A>G		intron_variant		5	NM_001164664.2	A2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38835 AN: 152014 Hom.: 5017 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.255 AC: 38848 AN: 152132 Hom.: 5020 Cov.: 33 AF XY: 0.256 AC XY: 19026 AN XY: 74366

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.261

Alfa AF: 0.256 Hom.: 1267

Bravo AF: 0.249

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.3
Dann	Benign	0.80

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: rs39861; hg19: chr5-66152258; COSMIC: COSV67795738;