NM_001172303.3:c.2267-3717C>A

Variant names:

• chr10-27177236-C-A
• rs7091723
• NM_001172303.3:c.2267-3717C>A

Variant summary

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

The NM_001172303.3(MASTL):​c.2267-3717C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 151,954 control chromosomes in the GnomAD database, including 27,972 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 0.60 (27972 hom., cov: 31)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.951
• Publications: 6 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):

• acyl-CoA binding domain containing protein 5 deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinal dystrophy with leukodystrophy

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.644 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.2267-3717C>A		intron	N/A	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.2267-565C>A		intron	N/A	NP_001307686.1
	MASTL	NM_001320756.2		c.2264-565C>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.2267-3717C>A		intron	N/A	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.2264-3717C>A		intron	N/A	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000969651.1		c.2267-565C>A		intron	N/A	ENSP00000639710.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91682 AN: 151836 Hom.: 27976 Cov.: 31

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.603 AC: 91688 AN: 151954 Hom.: 27972 Cov.: 31 AF XY: 0.602 AC XY: 44725 AN XY: 74274

African (AFR) AF: 0.562 AC: 23273 AN: 41436

American (AMR) AF: 0.570 AC: 8686 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3470

East Asian (EAS) AF: 0.425 AC: 2200 AN: 5174

South Asian (SAS) AF: 0.477 AC: 2298 AN: 4816

European-Finnish (FIN) AF: 0.662 AC: 6987 AN: 10552

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44084 AN: 67964

Other (OTH) AF: 0.587 AC: 1237 AN: 2108

Alfa AF: 0.628 Hom.: 3949

Bravo AF: 0.596

Asia WGS AF: 0.445 AC: 1550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.5
DANN	Benign	0.20
PhyloP100		0.95
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: rs7091723; hg19: chr10-27466165;