10-27186565-T-C

Variant names:

• chr10-27186565-T-C
• rs10764686
• NM_001172303.3:c.*29T>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.*29T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 1,576,432 control chromosomes in the GnomAD database, including 293,073 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (21701 hom., cov: 31)
  • Exomes 𝑓: 0.61 (271372 hom.)
• Consequence: MASTL NM_001172303.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.553
• Publications: 29 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=-0.68).
• BP6: Variant 10-27186565-T-C is Benign according to our data. Variant chr10-27186565-T-C is described in ClinVar as Benign. ClinVar VariationId is 262110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	NM_001172303.3	MANE Select	c.*29T>C		3_prime_UTR	Exon 12 of 12	NP_001165774.1
	MASTL	NR_135469.2		n.2602T>C		non_coding_transcript_exon	Exon 11 of 11
	MASTL	NM_001320757.2		c.*29T>C		3_prime_UTR	Exon 13 of 13	NP_001307686.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.*29T>C		3_prime_UTR	Exon 12 of 12	ENSP00000365107.5
	MASTL	ENST00000375946.8	TSL:1	c.*29T>C		3_prime_UTR	Exon 12 of 12	ENSP00000365113.4
	MASTL	ENST00000342386.10	TSL:2	c.*29T>C		3_prime_UTR	Exon 11 of 11	ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76005 AN: 151812 Hom.: 21710 Cov.: 31

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.522

GnomAD2 exomes AF: 0.563 AC: 141519 AN: 251308 AF XY: 0.569

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.579

Gnomad EAS exome AF: 0.435

Gnomad FIN exome AF: 0.663

Gnomad NFE exome AF: 0.648

Gnomad OTH exome AF: 0.602

GnomAD4 exome AF: 0.610 AC: 868883 AN: 1424502 Hom.: 271372 Cov.: 27 AF XY: 0.609 AC XY: 432863 AN XY: 711138

African (AFR) AF: 0.191 AC: 6309 AN: 32948

American (AMR) AF: 0.518 AC: 23132 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 14953 AN: 25920

East Asian (EAS) AF: 0.428 AC: 16920 AN: 39518

South Asian (SAS) AF: 0.488 AC: 41780 AN: 85564

European-Finnish (FIN) AF: 0.661 AC: 35258 AN: 53334

Middle Eastern (MID) AF: 0.556 AC: 3168 AN: 5700

European-Non Finnish (NFE) AF: 0.643 AC: 692937 AN: 1077632

Other (OTH) AF: 0.581 AC: 34426 AN: 59212

GnomAD4 genome AF: 0.500 AC: 75992 AN: 151930 Hom.: 21701 Cov.: 31 AF XY: 0.503 AC XY: 37367 AN XY: 74258

African (AFR) AF: 0.206 AC: 8555 AN: 41446

American (AMR) AF: 0.532 AC: 8103 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2056 AN: 3468

East Asian (EAS) AF: 0.439 AC: 2265 AN: 5160

South Asian (SAS) AF: 0.477 AC: 2295 AN: 4812

European-Finnish (FIN) AF: 0.662 AC: 6973 AN: 10540

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.646 AC: 43926 AN: 67956

Other (OTH) AF: 0.516 AC: 1089 AN: 2112

Alfa AF: 0.586 Hom.: 35819

Bravo AF: 0.478

Asia WGS AF: 0.434 AC: 1509 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.2
DANN	Benign	0.87
PhyloP100		0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs10764686; hg19: chr10-27475494; COSMIC: COSV60909982;