10-27154946-C-T

Position:

• chr10-27154946-C-T

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.-481C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 166,212 control chromosomes in the GnomAD database, including 534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (493 hom., cov: 32)
  • Exomes 𝑓: 0.056 (41 hom.)
• Consequence: MASTL ENST00000375946.8 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.799

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=-0.73).
• BP6: Variant 10-27154946-C-T is Benign according to our data. Variant chr10-27154946-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 299774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MASTL	XM_017016853.3	c.-243C>T		5_prime_UTR_variant	1/13
MASTL	XM_047425916.1	c.-243C>T		5_prime_UTR_variant	1/12
MASTL	XM_047425917.1	c.-243C>T		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MASTL	ENST00000375946.8	c.-481C>T		5_prime_UTR_variant	1/12	1		A1
YME1L1	ENST00000477432.1	c.-736G>A		5_prime_UTR_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11358 AN: 152042 Hom.: 492 Cov.: 32

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.0556 AC: 781 AN: 14052 Hom.: 41 Cov.: 0 AF XY: 0.0586 AC XY: 431 AN XY: 7358

Gnomad4 AFR exome AF: 0.0970

Gnomad4 AMR exome AF: 0.0392

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.121

Gnomad4 SAS exome AF: 0.111

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0407

Gnomad4 OTH exome AF: 0.0617

GnomAD4 genome AF: 0.0748 AC: 11379 AN: 152160 Hom.: 493 Cov.: 32 AF XY: 0.0789 AC XY: 5867 AN XY: 74384

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0712 Hom.: 56

Bravo AF: 0.0708

Asia WGS AF: 0.154 AC: 535 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	-0.73
CADD	Benign	11
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28365962; hg19: chr10-27443875;