rs73598041

Variant names:

• chr10-27186346-T-C
• rs73598041
• NM_001172303.3:c.2483-33T>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.2483-33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 1,592,828 control chromosomes in the GnomAD database, including 2,009 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (257 hom., cov: 33)
  • Exomes 𝑓: 0.047 (1752 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.14
• 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]

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]

ACBD5 Gene-Disease associations (from GenCC):

• retinal dystrophy with leukodystrophy

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• acyl-CoA binding domain containing protein 5 deficiency

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-27186346-T-C is Benign according to our data. Variant chr10-27186346-T-C is described in ClinVar as Benign. ClinVar VariationId is 262121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.2483-33T>C		intron_variant	Intron 11 of 11	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.2483-33T>C		intron_variant	Intron 11 of 11	1	NM_001172303.3	ENSP00000365107.5

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8490 AN: 152180 Hom.: 255 Cov.: 33

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0330

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.0323

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0440

GnomAD2 exomes AF: 0.0439 AC: 11018 AN: 250982 AF XY: 0.0435

Gnomad AFR exome AF: 0.0832

Gnomad AMR exome AF: 0.0188

Gnomad ASJ exome AF: 0.0631

Gnomad EAS exome AF: 0.00348

Gnomad FIN exome AF: 0.0553

Gnomad NFE exome AF: 0.0512

Gnomad OTH exome AF: 0.0415

GnomAD4 exome AF: 0.0470 AC: 67675 AN: 1440530 Hom.: 1752 Cov.: 28 AF XY: 0.0467 AC XY: 33539 AN XY: 718024

African (AFR) AF: 0.0847 AC: 2796 AN: 33004

American (AMR) AF: 0.0198 AC: 886 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0636 AC: 1655 AN: 26028

East Asian (EAS) AF: 0.00195 AC: 77 AN: 39580

South Asian (SAS) AF: 0.0350 AC: 3003 AN: 85820

European-Finnish (FIN) AF: 0.0557 AC: 2975 AN: 53398

Middle Eastern (MID) AF: 0.0405 AC: 232 AN: 5728

European-Non Finnish (NFE) AF: 0.0487 AC: 53198 AN: 1092522

Other (OTH) AF: 0.0477 AC: 2853 AN: 59760

GnomAD4 genome AF: 0.0559 AC: 8511 AN: 152298 Hom.: 257 Cov.: 33 AF XY: 0.0547 AC XY: 4076 AN XY: 74474

African (AFR) AF: 0.0825 AC: 3430 AN: 41552

American (AMR) AF: 0.0330 AC: 505 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0674 AC: 234 AN: 3472

East Asian (EAS) AF: 0.00308 AC: 16 AN: 5192

South Asian (SAS) AF: 0.0321 AC: 155 AN: 4826

European-Finnish (FIN) AF: 0.0519 AC: 551 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0514 AC: 3497 AN: 68024

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0580 Hom.: 98

Bravo AF: 0.0561

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.46
PhyloP100		1.1
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: rs73598041; hg19: chr10-27475275;