rs257712

Positions:

• chr5-66793249-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001164664.2(MAST4):​c.642+4455G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,138 control chromosomes in the GnomAD database, including 18,713 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 0.49 (18713 hom., cov: 33)
• Consequence: MAST4 NM_001164664.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST4	NM_001164664.2	c.642+4455G>A		intron_variant		ENST00000403625.7	NP_001158136.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST4	ENST00000403625.7	c.642+4455G>A		intron_variant		5	NM_001164664.2	ENSP00000385727	A2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74833 AN: 152020 Hom.: 18688 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.492 AC: 74901 AN: 152138 Hom.: 18713 Cov.: 33 AF XY: 0.492 AC XY: 36597 AN XY: 74376

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.656

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.490

Alfa AF: 0.494 Hom.: 3007

Bravo AF: 0.480

Asia WGS AF: 0.620 AC: 2152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	13
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs257712; hg19: chr5-66089077; COSMIC: COSV68233682; COSMIC: COSV68233682;