Genetic Variant MASTL:c.-27T>G (chr10-27155400-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001172303.3(MASTL):c.-27T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

MASTL
NM_001172303.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.35

Publications

10 publications found

Variant links:

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]

MASTL links:

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]

YME1L1 Gene-Disease associations (from GenCC):

autosomal recessive optic atrophy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
optic atrophy 11
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

YME1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MASTL	NM_001172303.3 link	c.-27T>G		5_prime_UTR_variant	Exon 1 of 12	ENST00000375940.9	NP_001165774.1	Q96GX5-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MASTL	ENST00000375940.9 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 12	1	NM_001172303.3	ENSP00000365107.5	Q96GX5-1
MASTL	ENST00000375946.8 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 12	1		ENSP00000365113.4	Q96GX5-3
MASTL	ENST00000342386.10 link	c.-27T>G	5_prime_UTR_variant	Exon 1 of 11	2		ENSP00000343446.5	Q96GX5-2
YME1L1	ENST00000477432.1 link	c.-1190A>C	upstream_gene_variant		1		ENSP00000473302.1	Q6PJ89

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000509

AC:

AN:

196508

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000922

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.01e-7

AC:

AN:

1426912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707286

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32526

American (AMR)

AF:

0.00

AC:

AN:

38842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25540

East Asian (EAS)

AF:

0.00

AC:

AN:

37750

South Asian (SAS)

AF:

0.00

AC:

AN:

83566

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4156

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096470

Other (OTH)

AF:

0.00

AC:

AN:

59016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

4629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.39

(source)

DANN

Benign

0.51

PhyloP100

-4.3

PromoterAI

-0.051

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over