NM_001393504.1:c.1695C>T

Variant names:

• chr19-18134702-C-T
• rs2270623
• NM_001393504.1:c.1695C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001393504.1(MAST3):​c.1695C>T​(p.Ile565Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,612,518 control chromosomes in the GnomAD database, including 228,970 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18230 hom., cov: 31)
  • Exomes 𝑓: 0.53 (210740 hom.)
• Consequence: MAST3 NM_001393504.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.730
• Publications: 23 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 19-18134702-C-T is Benign according to our data. Variant chr19-18134702-C-T is described in ClinVar as Benign. ClinVar VariationId is 1179690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	NM_001393504.1	MANE Select	c.1695C>T	p.Ile565Ile	synonymous	Exon 16 of 28	NP_001380433.1	A0A8I5KST9
	MAST3	NM_001393501.1		c.1719C>T	p.Ile573Ile	synonymous	Exon 17 of 29	NP_001380430.1
	MAST3	NM_001393502.1		c.1698C>T	p.Ile566Ile	synonymous	Exon 16 of 28	NP_001380431.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST3	ENST00000687212.1	MANE Select	c.1695C>T	p.Ile565Ile	synonymous	Exon 16 of 28	ENSP00000509890.1	A0A8I5KST9
	MAST3	ENST00000262811.10	TSL:1	c.1608C>T	p.Ile536Ile	synonymous	Exon 15 of 27	ENSP00000262811.4	O60307
	MAST3	ENST00000697701.1		c.1674C>T	p.Ile558Ile	synonymous	Exon 15 of 27	ENSP00000513408.1	A0A8V8TLL8

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73132 AN: 151906 Hom.: 18231 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.526

Gnomad OTH AF: 0.472

GnomAD2 exomes AF: 0.534 AC: 131943 AN: 246996 AF XY: 0.540

Gnomad AFR exome AF: 0.341

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.447

Gnomad EAS exome AF: 0.686

Gnomad FIN exome AF: 0.506

Gnomad NFE exome AF: 0.526

Gnomad OTH exome AF: 0.517

GnomAD4 exome AF: 0.534 AC: 780142 AN: 1460494 Hom.: 210740 Cov.: 72 AF XY: 0.537 AC XY: 389921 AN XY: 726440

African (AFR) AF: 0.334 AC: 11195 AN: 33472

American (AMR) AF: 0.513 AC: 22810 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 11859 AN: 26100

East Asian (EAS) AF: 0.698 AC: 27687 AN: 39648

South Asian (SAS) AF: 0.639 AC: 55027 AN: 86160

European-Finnish (FIN) AF: 0.505 AC: 26904 AN: 53318

Middle Eastern (MID) AF: 0.436 AC: 2515 AN: 5766

European-Non Finnish (NFE) AF: 0.532 AC: 590675 AN: 1111274

Other (OTH) AF: 0.522 AC: 31470 AN: 60326

GnomAD4 genome AF: 0.481 AC: 73150 AN: 152024 Hom.: 18230 Cov.: 31 AF XY: 0.482 AC XY: 35784 AN XY: 74296

African (AFR) AF: 0.348 AC: 14445 AN: 41480

American (AMR) AF: 0.495 AC: 7554 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1652 AN: 3470

East Asian (EAS) AF: 0.684 AC: 3527 AN: 5158

South Asian (SAS) AF: 0.646 AC: 3113 AN: 4816

European-Finnish (FIN) AF: 0.505 AC: 5338 AN: 10568

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.526 AC: 35712 AN: 67956

Other (OTH) AF: 0.476 AC: 1006 AN: 2112

Alfa AF: 0.494 Hom.: 29300

Bravo AF: 0.471

Asia WGS AF: 0.631 AC: 2193 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	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: rs2270623; hg19: chr19-18245512; COSMIC: COSV53217649; COSMIC: COSV53217649;