rs788238

Variant names:

• chr10-27167074-G-A
• rs788238
• NM_001172303.3:c.812-28G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27167074-G-A
• chr10-27167074-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001172303.3(MASTL):​c.812-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.999 in 1,593,372 control chromosomes in the GnomAD database, including 794,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (75192 hom., cov: 31)
  • Exomes 𝑓: 1.0 (719557 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.101
• Publications: 7 publications found

Genes affected

MASTL (HGNC:19042): (microtubule associated serine/threonine kinase like) This gene encodes a microtubule-associated serine/threonine kinase. Mutations at this locus have been associated with autosomal dominant thrombocytopenia, also known as thrombocytopenia-2. Alternatively spliced transcript variants have been described for this locus. [provided by RefSeq, Feb 2010]

MASTL Gene-Disease associations (from GenCC):

• autosomal thrombocytopenia with normal platelets

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thrombocytopenia

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-27167074-G-A is Benign according to our data. Variant chr10-27167074-G-A is described in ClinVar as Benign. ClinVar VariationId is 262127.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172303.3. 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
	MASTL	NM_001172303.3	MANE Select	c.812-28G>A		intron	N/A	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.812-28G>A		intron	N/A	NP_001307686.1
	MASTL	NM_001320756.2		c.812-28G>A		intron	N/A	NP_001307685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.812-28G>A		intron	N/A	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.812-28G>A		intron	N/A	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000969651.1		c.812-28G>A		intron	N/A	ENSP00000639710.1

Frequencies

GnomAD3 genomes AF: 0.994 AC: 151220 AN: 152182 Hom.: 75138 Cov.: 31

Gnomad AFR AF: 0.978

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.997

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.995

GnomAD2 exomes AF: 0.998 AC: 250720 AN: 251112 AF XY: 0.999

Gnomad AFR exome AF: 0.979

Gnomad AMR exome AF: 0.999

Gnomad ASJ exome AF: 1.00

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 1.00

Gnomad OTH exome AF: 1.00

GnomAD4 exome AF: 0.999 AC: 1440077 AN: 1441072 Hom.: 719557 Cov.: 26 AF XY: 0.999 AC XY: 717962 AN XY: 718386

African (AFR) AF: 0.976 AC: 32194 AN: 32994

American (AMR) AF: 0.999 AC: 44645 AN: 44704

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 26012 AN: 26012

East Asian (EAS) AF: 1.00 AC: 39552 AN: 39552

South Asian (SAS) AF: 1.00 AC: 85806 AN: 85808

European-Finnish (FIN) AF: 1.00 AC: 53250 AN: 53250

Middle Eastern (MID) AF: 0.999 AC: 5727 AN: 5732

European-Non Finnish (NFE) AF: 1.00 AC: 1093274 AN: 1093306

Other (OTH) AF: 0.998 AC: 59617 AN: 59714

GnomAD4 genome AF: 0.994 AC: 151333 AN: 152300 Hom.: 75192 Cov.: 31 AF XY: 0.994 AC XY: 74009 AN XY: 74462

African (AFR) AF: 0.978 AC: 40642 AN: 41552

American (AMR) AF: 0.997 AC: 15246 AN: 15290

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5176 AN: 5176

South Asian (SAS) AF: 1.00 AC: 4821 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10623 AN: 10624

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 68047 AN: 68048

Other (OTH) AF: 0.995 AC: 2100 AN: 2110

Alfa AF: 0.997 Hom.: 14425

Bravo AF: 0.993

Asia WGS AF: 0.996 AC: 3464 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.39
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs788238; hg19: chr10-27456003;