10-27155311-C-CG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000375946.8(MASTL):c.-112dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0267 in 1,030,070 control chromosomes in the GnomAD database, including 466 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.023 (59 hom., cov: 31)
  • Exomes 𝑓: 0.027 (407 hom.)
• Consequence: MASTL ENST00000375946.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.51

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]

YME1L1 (HGNC:12843): (YME1 like 1 ATPase) The protein encoded by this gene is the human ortholog of yeast mitochondrial AAA metalloprotease, Yme1p. It is localized in the mitochondria and can functionally complement a yme1 disruptant yeast strain. It is proposed that this gene plays a role in mitochondrial protein metabolism and could be involved in mitochondrial pathologies. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-27155311-C-CG is Benign according to our data. Variant chr10-27155311-C-CG is described in ClinVar as [Likely_benign]. Clinvar id is 299783.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0228 (3473/152160) while in subpopulation NFE AF= 0.0344 (2336/67980). AF 95% confidence interval is 0.0332. There are 59 homozygotes in gnomad4. There are 1675 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 3475 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	NM_001172303.3			upstream_gene_variant		ENST00000375940.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375946.8	c.-112dup		5_prime_UTR_variant	1/12	1		A1
MASTL	ENST00000375940.9			upstream_gene_variant		1	NM_001172303.3	P5
YME1L1	ENST00000477432.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3475 AN: 152042 Hom.: 59 Cov.: 31

Gnomad AFR AF: 0.00531

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0265

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00974

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0274 AC: 24016 AN: 877910 Hom.: 407 Cov.: 12 AF XY: 0.0270 AC XY: 11896 AN XY: 441310

Gnomad4 AFR exome AF: 0.00451

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.0271

Gnomad4 EAS exome AF: 0.0000912

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.0290

Gnomad4 NFE exome AF: 0.0312

Gnomad4 OTH exome AF: 0.0259

GnomAD4 genome AF: 0.0228 AC: 3473 AN: 152160 Hom.: 59 Cov.: 31 AF XY: 0.0225 AC XY: 1675 AN XY: 74394

Gnomad4 AFR AF: 0.00527

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0265

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00975

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0344

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0287 Hom.: 10

Bravo AF: 0.0221

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thrombocytopenia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs150868633; hg19: chr10-27444240;