10-27155415-T-G

Variant names:

• chr10-27155415-T-G
• rs7907988
• NM_001172303.3:c.-12T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375940.9(MASTL):​c.-12T>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 0.832 in 1,599,164 control chromosomes in the GnomAD database, including 555,079 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (54586 hom., cov: 32)
  • Exomes 𝑓: 0.83 (500493 hom.)
• Consequence: MASTL ENST00000375940.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.987
• Publications: 23 publications found

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]

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-27155415-T-G is Benign according to our data. Variant chr10-27155415-T-G is described in ClinVar as Benign. ClinVar VariationId is 262111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375940.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	NM_001172303.3	MANE Select	c.-12T>G		5_prime_UTR	Exon 1 of 12	NP_001165774.1
	MASTL	NR_135469.2		n.64T>G		non_coding_transcript_exon	Exon 1 of 11
	MASTL	NM_001320757.2		c.-12T>G		5_prime_UTR	Exon 1 of 13	NP_001307686.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MASTL	ENST00000375940.9	TSL:1 MANE Select	c.-12T>G		5_prime_UTR	Exon 1 of 12	ENSP00000365107.5
	MASTL	ENST00000375946.8	TSL:1	c.-12T>G		5_prime_UTR	Exon 1 of 12	ENSP00000365113.4
	MASTL	ENST00000342386.10	TSL:2	c.-12T>G		5_prime_UTR	Exon 1 of 11	ENSP00000343446.5

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128472 AN: 152020 Hom.: 54559 Cov.: 32

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.821

GnomAD2 exomes AF: 0.842 AC: 189205 AN: 224638 AF XY: 0.844

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.842

Gnomad EAS exome AF: 0.992

Gnomad FIN exome AF: 0.933

Gnomad NFE exome AF: 0.827

Gnomad OTH exome AF: 0.830

GnomAD4 exome AF: 0.831 AC: 1202003 AN: 1447026 Hom.: 500493 Cov.: 44 AF XY: 0.831 AC XY: 597913 AN XY: 719118

African (AFR) AF: 0.864 AC: 28665 AN: 33166

American (AMR) AF: 0.734 AC: 30719 AN: 41832

Ashkenazi Jewish (ASJ) AF: 0.842 AC: 21807 AN: 25914

East Asian (EAS) AF: 0.985 AC: 38425 AN: 39014

South Asian (SAS) AF: 0.855 AC: 72773 AN: 85148

European-Finnish (FIN) AF: 0.926 AC: 47830 AN: 51660

Middle Eastern (MID) AF: 0.803 AC: 3511 AN: 4372

European-Non Finnish (NFE) AF: 0.821 AC: 908338 AN: 1106194

Other (OTH) AF: 0.836 AC: 49935 AN: 59726

GnomAD4 genome AF: 0.845 AC: 128549 AN: 152138 Hom.: 54586 Cov.: 32 AF XY: 0.853 AC XY: 63407 AN XY: 74370

African (AFR) AF: 0.866 AC: 35973 AN: 41522

American (AMR) AF: 0.772 AC: 11798 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2932 AN: 3468

East Asian (EAS) AF: 0.989 AC: 5093 AN: 5148

South Asian (SAS) AF: 0.865 AC: 4171 AN: 4822

European-Finnish (FIN) AF: 0.932 AC: 9881 AN: 10606

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 56011 AN: 67970

Other (OTH) AF: 0.823 AC: 1734 AN: 2108

Alfa AF: 0.821 Hom.: 64651

Bravo AF: 0.833

Asia WGS AF: 0.915 AC: 3182 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Thrombocytopenia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.42
PhyloP100		-0.99
PromoterAI		0.022	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7907988; hg19: chr10-27444344;