10-27169750-C-T

Position:

• chr10-27169750-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001172303.3(MASTL):​c.985-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0798 in 152,112 control chromosomes in the GnomAD database, including 717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.080 (717 hom., cov: 32)
• Consequence: MASTL NM_001172303.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.379

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-27169750-C-T is Benign according to our data. Variant chr10-27169750-C-T is described in ClinVar as [Benign]. Clinvar id is 1284205.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	NM_001172303.3	c.985-194C>T		intron_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375940.9	c.985-194C>T		intron_variant		1	NM_001172303.3	P5
MASTL	ENST00000375946.8	c.985-194C>T		intron_variant		1		A1
ACBD5	ENST00000677440.1	c.*481G>A		3_prime_UTR_variant	13/13
MASTL	ENST00000342386.10	c.985-194C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12117 AN: 151994 Hom.: 705 Cov.: 32

Gnomad AFR AF: 0.0186

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0873

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.0885

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

GnomAD4 genome AF: 0.0798 AC: 12140 AN: 152112 Hom.: 717 Cov.: 32 AF XY: 0.0865 AC XY: 6431 AN XY: 74346

Gnomad4 AFR AF: 0.0186

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0873

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.0985

Alfa AF: 0.0710 Hom.: 90

Bravo AF: 0.0740

Asia WGS AF: 0.239 AC: 828 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs34743977; hg19: chr10-27458679;