10-27155415-T-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001172303.3(MASTL):​c.-12T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,447,560 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: 0.0000083 (0 hom.)
• Consequence: MASTL NM_001172303.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172303.3. 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>A		5_prime_UTR	Exon 1 of 12	NP_001165774.1
	MASTL	NR_135469.2		n.64T>A		non_coding_transcript_exon	Exon 1 of 11
	MASTL	NM_001320757.2		c.-12T>A		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>A		5_prime_UTR	Exon 1 of 12	ENSP00000365107.5
	MASTL	ENST00000375946.8	TSL:1	c.-12T>A		5_prime_UTR	Exon 1 of 12	ENSP00000365113.4
	MASTL	ENST00000342386.10	TSL:2	c.-12T>A		5_prime_UTR	Exon 1 of 11	ENSP00000343446.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000829 AC: 12 AN: 1447560 Hom.: 0 Cov.: 44 AF XY: 0.00000834 AC XY: 6 AN XY: 719382

African (AFR) AF: 0.00 AC: 0 AN: 33178

American (AMR) AF: 0.00 AC: 0 AN: 41864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25918

East Asian (EAS) AF: 0.00 AC: 0 AN: 39018

South Asian (SAS) AF: 0.00 AC: 0 AN: 85164

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51680

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4374

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1106618

Other (OTH) AF: 0.00 AC: 0 AN: 59746

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.8
DANN	Benign	0.32
PhyloP100		-0.99
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;