rs10741130

Variant names:

• chr10-27186515-T-C
• rs10741130
• NM_001172303.3:c.2619T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-27186515-T-C
• chr10-27186515-T-A
• chr10-27186515-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001172303.3(MASTL):​c.2619T>C​(p.Thr873Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,612,818 control chromosomes in the GnomAD database, including 323,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.61 (28393 hom., cov: 32)
  • Exomes 𝑓: 0.63 (294887 hom.)
• Consequence: MASTL NM_001172303.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.27
• Publications: 33 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-27186515-T-C is Benign according to our data. Variant chr10-27186515-T-C is described in ClinVar as Benign. ClinVar VariationId is 262122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.27 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 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.2619T>C	p.Thr873Thr	synonymous	Exon 12 of 12	NP_001165774.1	Q96GX5-1
	MASTL	NM_001320757.2		c.2634T>C	p.Thr878Thr	synonymous	Exon 13 of 13	NP_001307686.1
	MASTL	NM_001320756.2		c.2631T>C	p.Thr877Thr	synonymous	Exon 13 of 13	NP_001307685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.2619T>C	p.Thr873Thr	synonymous	Exon 12 of 12	ENSP00000365107.5	Q96GX5-1
	MASTL	ENST00000375946.8	TSL:1	c.2616T>C	p.Thr872Thr	synonymous	Exon 12 of 12	ENSP00000365113.4	Q96GX5-3
	MASTL	ENST00000969651.1		c.2634T>C	p.Thr878Thr	synonymous	Exon 13 of 13	ENSP00000639710.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92341 AN: 151806 Hom.: 28395 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.596

GnomAD2 exomes AF: 0.596 AC: 149846 AN: 251410 AF XY: 0.595

Gnomad AFR exome AF: 0.558

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.436

Gnomad FIN exome AF: 0.670

Gnomad NFE exome AF: 0.658

Gnomad OTH exome AF: 0.620

GnomAD4 exome AF: 0.632 AC: 923262 AN: 1460894 Hom.: 294887 Cov.: 48 AF XY: 0.629 AC XY: 456836 AN XY: 726812

African (AFR) AF: 0.564 AC: 18881 AN: 33462

American (AMR) AF: 0.538 AC: 24071 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 16166 AN: 26126

East Asian (EAS) AF: 0.429 AC: 17014 AN: 39684

South Asian (SAS) AF: 0.491 AC: 42301 AN: 86240

European-Finnish (FIN) AF: 0.670 AC: 35781 AN: 53414

Middle Eastern (MID) AF: 0.579 AC: 3338 AN: 5766

European-Non Finnish (NFE) AF: 0.656 AC: 728587 AN: 1111118

Other (OTH) AF: 0.615 AC: 37123 AN: 60362

GnomAD4 genome AF: 0.608 AC: 92350 AN: 151924 Hom.: 28393 Cov.: 32 AF XY: 0.607 AC XY: 45029 AN XY: 74244

African (AFR) AF: 0.563 AC: 23314 AN: 41398

American (AMR) AF: 0.571 AC: 8698 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2183 AN: 3470

East Asian (EAS) AF: 0.440 AC: 2269 AN: 5156

South Asian (SAS) AF: 0.477 AC: 2297 AN: 4816

European-Finnish (FIN) AF: 0.669 AC: 7070 AN: 10568

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

European-Non Finnish (NFE) AF: 0.655 AC: 44534 AN: 67974

Other (OTH) AF: 0.589 AC: 1243 AN: 2112

Alfa AF: 0.628 Hom.: 16753

Bravo AF: 0.600

Asia WGS AF: 0.448 AC: 1558 AN: 3478

EpiCase AF: 0.650

EpiControl AF: 0.646

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.38
DANN	Benign	0.50
PhyloP100		-1.3
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: rs10741130; hg19: chr10-27475444; COSMIC: COSV60909974;