rs41282228

Variant names:

• chr10-27173132-G-A
• rs41282228
• NM_001172303.3:c.2139G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-27173132-G-A
• chr10-27173132-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001172303.3(MASTL):​c.2139G>A​(p.Gln713Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0167 in 1,614,040 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (22 hom., cov: 31)
  • Exomes 𝑓: 0.017 (309 hom.)
• Consequence: MASTL NM_001172303.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0870

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]

ACBD5 (HGNC:23338): (acyl-CoA binding domain containing 5) This gene encodes a member of the acyl-Coenzyme A binding protein family, known to function in the transport and distribution of long chain acyl-Coenzyme A in cells. This gene may play a role in the differentiation of megakaryocytes and formation of platelets. A related protein in yeast is involved in autophagy of peroxisomes. A mutation in this gene has been associated with autosomal dominant thrombocytopenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 10-27173132-G-A is Benign according to our data. Variant chr10-27173132-G-A is described in ClinVar as [Benign]. Clinvar id is 262119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.087 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0119 (1817/152242) while in subpopulation SAS AF= 0.0336 (162/4820). AF 95% confidence interval is 0.0294. There are 22 homozygotes in gnomad4. There are 884 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1817 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.2139G>A	p.Gln713Gln	synonymous_variant	Exon 9 of 12	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.2139G>A	p.Gln713Gln	synonymous_variant	Exon 9 of 12	1	NM_001172303.3	ENSP00000365107.5

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1818 AN: 152124 Hom.: 22 Cov.: 31

Gnomad AFR AF: 0.00268

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0159 AC: 3989 AN: 251404 Hom.: 74 AF XY: 0.0178 AC XY: 2413 AN XY: 135870

Gnomad AFR exome AF: 0.00295

Gnomad AMR exome AF: 0.00376

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.000217

Gnomad SAS exome AF: 0.0387

Gnomad FIN exome AF: 0.0238

Gnomad NFE exome AF: 0.0160

Gnomad OTH exome AF: 0.0173

GnomAD4 exome AF: 0.0171 AC: 25069 AN: 1461798 Hom.: 309 Cov.: 31 AF XY: 0.0181 AC XY: 13132 AN XY: 727214

Gnomad4 AFR exome AF: 0.00257

Gnomad4 AMR exome AF: 0.00425

Gnomad4 ASJ exome AF: 0.0166

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0383

Gnomad4 FIN exome AF: 0.0272

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.0119 AC: 1817 AN: 152242 Hom.: 22 Cov.: 31 AF XY: 0.0119 AC XY: 884 AN XY: 74430

Gnomad4 AFR AF: 0.00267

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0336

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0156

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0148 Hom.: 7

Bravo AF: 0.00976

Asia WGS AF: 0.0130 AC: 45 AN: 3478

EpiCase AF: 0.0156

EpiControl AF: 0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Thrombocytopenia Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.48
DANN	Benign	0.63

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: rs41282228; hg19: chr10-27462061;