rs796052141

Positions:

• chr10-27126786-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP6

The ENST00000376016.8(YME1L1):​c.859G>A​(p.Val287Met) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YME1L1 ENST00000376016.8 missense, splice_region
• Scores: Splicing: ADA: 0.9992
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 6.77

Genes affected

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), YME1L1. . Gene score misZ 2.5125 (greater than the threshold 3.09). Trascript score misZ 3.2015 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive optic atrophy, optic atrophy 11.
• BP6: Variant 10-27126786-C-T is Benign according to our data. Variant chr10-27126786-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 207832.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YME1L1	NM_014263.4	c.859G>A	p.Val287Met	missense_variant, splice_region_variant	9/19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3	c.1030G>A	p.Val344Met	missense_variant, splice_region_variant	10/20		NP_647473.1
YME1L1	NM_001253866.2	c.760G>A	p.Val254Met	missense_variant, splice_region_variant	8/18		NP_001240795.1
YME1L1	XM_011519300.4	c.931G>A	p.Val311Met	missense_variant, splice_region_variant	9/19		XP_011517602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YME1L1	ENST00000376016.8	c.859G>A	p.Val287Met	missense_variant, splice_region_variant	9/19	1	NM_014263.4	ENSP00000365184	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	.;T;.;T;.
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.49	T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	.;L;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.8	.;N;N;D;.
REVEL	Benign	0.18
Sift	Benign	0.062	.;T;T;D;.
Sift4G	Benign	0.12	T;T;T;T;.
Polyphen		0.38, 1.0	.;B;D;.;.
Vest4		0.43
MutPred		0.36		.;Loss of catalytic residue at V344 (P = 0.0342);.;Loss of catalytic residue at V344 (P = 0.0342);.;
MVP		0.72
MPC		1.1
ClinPred		0.94	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.90
SpliceAI score (max)		0.10		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: rs796052141; hg19: chr10-27415715;