10-27155228-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375946.8(MASTL):c.-199G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 611,014 control chromosomes in the GnomAD database, including 814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (258 hom., cov: 32)
  • Exomes 𝑓: 0.045 (556 hom.)
• Consequence: MASTL ENST00000375946.8 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-27155228-G-C is Benign according to our data. Variant chr10-27155228-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 299780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0802 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	XM_017016853.3	c.39+1G>C		splice_donor_variant
MASTL	XM_047425916.1	c.39+1G>C		splice_donor_variant
MASTL	XM_047425917.1	c.39+1G>C		splice_donor_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375946.8	c.-199G>C		5_prime_UTR_variant	1/12	1		A1
YME1L1	ENST00000477432.1	c.-1018C>G		5_prime_UTR_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.0558 AC: 8498 AN: 152172 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0331

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0452 AC: 20740 AN: 458724 Hom.: 556 Cov.: 5 AF XY: 0.0448 AC XY: 10868 AN XY: 242700

Gnomad4 AFR exome AF: 0.0823

Gnomad4 AMR exome AF: 0.0231

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.00156

Gnomad4 SAS exome AF: 0.0347

Gnomad4 FIN exome AF: 0.0548

Gnomad4 NFE exome AF: 0.0496

Gnomad4 OTH exome AF: 0.0447

GnomAD4 genome AF: 0.0559 AC: 8519 AN: 152290 Hom.: 258 Cov.: 32 AF XY: 0.0548 AC XY: 4082 AN XY: 74482

Gnomad4 AFR AF: 0.0826

Gnomad4 AMR AF: 0.0331

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.00310

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0284 Hom.: 22

Bravo AF: 0.0561

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Thrombocytopenia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.2
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs41282216; hg19: chr10-27444157;