NM_001393504.1:c.40-3876T>C

Variant names:

• chr19-18103711-T-C
• rs11668601
• NM_001393504.1:c.40-3876T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393504.1(MAST3):​c.40-3876T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,146 control chromosomes in the GnomAD database, including 3,016 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 0.18 (3016 hom., cov: 31)
• Consequence: MAST3 NM_001393504.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 7 publications found

Genes affected

MAST3 (HGNC:19036): (microtubule associated serine/threonine kinase 3) Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in cytoskeleton organization; intracellular signal transduction; and peptidyl-serine phosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

MAST3 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 108

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393504.1. 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
	MAST3	NM_001393504.1	MANE Select	c.40-3876T>C		intron	N/A	NP_001380433.1
	MAST3	NM_001393501.1		c.40-3876T>C		intron	N/A	NP_001380430.1
	MAST3	NM_001393502.1		c.40-3876T>C		intron	N/A	NP_001380431.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.40-3876T>C		intron	N/A	ENSP00000509890.1
	MAST3	ENST00000262811.10	TSL:1	c.40-3876T>C		intron	N/A	ENSP00000262811.4
	MAST3	ENST00000697700.2		c.40-3876T>C		intron	N/A	ENSP00000513407.2

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27129 AN: 152028 Hom.: 3014 Cov.: 31

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.178 AC: 27129 AN: 152146 Hom.: 3016 Cov.: 31 AF XY: 0.179 AC XY: 13322 AN XY: 74364

African (AFR) AF: 0.0438 AC: 1820 AN: 41556

American (AMR) AF: 0.166 AC: 2529 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 878 AN: 3468

East Asian (EAS) AF: 0.122 AC: 631 AN: 5172

South Asian (SAS) AF: 0.167 AC: 805 AN: 4824

European-Finnish (FIN) AF: 0.267 AC: 2825 AN: 10562

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 17007 AN: 67988

Other (OTH) AF: 0.197 AC: 414 AN: 2106

Alfa AF: 0.127 Hom.: 243

Bravo AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11668601; hg19: chr19-18214521;