10-27171103-A-C

Variant names:

• chr10-27171103-A-C
• rs141066111
• NM_001172303.3:c.2124+20A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001172303.3(MASTL):​c.2124+20A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00073 in 1,608,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (0 hom.)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.357
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 10-27171103-A-C is Benign according to our data. Variant chr10-27171103-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 262118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 62 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	NM_001172303.3	MANE Select	c.2124+20A>C		intron	N/A	NP_001165774.1
	MASTL	NM_001320757.2		c.2124+20A>C		intron	N/A	NP_001307686.1
	MASTL	NM_001320756.2		c.2124+20A>C		intron	N/A	NP_001307685.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.2124+20A>C		intron	N/A	ENSP00000365107.5
	MASTL	ENST00000375946.8	TSL:1	c.2124+20A>C		intron	N/A	ENSP00000365113.4
	MASTL	ENST00000342386.10	TSL:2	c.2124+20A>C		intron	N/A	ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000496 AC: 124 AN: 249778 AF XY: 0.000458

Gnomad AFR exome AF: 0.000194

Gnomad AMR exome AF: 0.000637

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000814

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000764 AC: 1113 AN: 1456560 Hom.: 0 Cov.: 31 AF XY: 0.000763 AC XY: 553 AN XY: 725024

African (AFR) AF: 0.000120 AC: 4 AN: 33370

American (AMR) AF: 0.000649 AC: 29 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86132

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53410

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.000910 AC: 1008 AN: 1107256

Other (OTH) AF: 0.000880 AC: 53 AN: 60202

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74444

African (AFR) AF: 0.000120 AC: 5 AN: 41562

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000765 AC: 52 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000769 Hom.: 0

Bravo AF: 0.000457

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.70
PhyloP100		0.36
Mutation Taster		=99/1	polymorphism

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: rs141066111; hg19: chr10-27460032;