rs788237

Variant names:

• chr10-27169003-C-T
• rs788237
• NM_001172303.3:c.985-941C>T

Variant summary

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

The NM_001172303.3(MASTL):​c.985-941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,874 control chromosomes in the GnomAD database, including 1,881 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 0.14 (1881 hom., cov: 31)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3	c.985-941C>T		intron_variant	Intron 7 of 11	ENST00000375940.9	NP_001165774.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MASTL	ENST00000375940.9	c.985-941C>T		intron_variant	Intron 7 of 11	1	NM_001172303.3	ENSP00000365107.5
MASTL	ENST00000375946.8	c.985-941C>T		intron_variant	Intron 7 of 11	1		ENSP00000365113.4
ACBD5	ENST00000677440.1	c.*1228G>A		3_prime_UTR_variant	Exon 13 of 13			ENSP00000504580.1
MASTL	ENST00000342386.10	c.985-941C>T		intron_variant	Intron 7 of 10	2		ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21835 AN: 151756 Hom.: 1873 Cov.: 31

Gnomad AFR AF: 0.0995

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0102

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.144 AC: 21863 AN: 151874 Hom.: 1881 Cov.: 31 AF XY: 0.136 AC XY: 10089 AN XY: 74206

African (AFR) AF: 0.0996 AC: 4125 AN: 41400

American (AMR) AF: 0.225 AC: 3428 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3468

East Asian (EAS) AF: 0.0103 AC: 53 AN: 5164

South Asian (SAS) AF: 0.112 AC: 538 AN: 4822

European-Finnish (FIN) AF: 0.0680 AC: 716 AN: 10528

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11879 AN: 67948

Other (OTH) AF: 0.171 AC: 361 AN: 2112

Alfa AF: 0.154 Hom.: 267

Bravo AF: 0.156

Asia WGS AF: 0.0670 AC: 235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.52
DANN	Benign	0.21
PhyloP100		-0.79
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: rs788237; hg19: chr10-27457932;