Variant rs1057519312 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5

The NM_014263.4(YME1L1):c.445C>T(p.Arg149Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

YME1L1
NM_014263.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.53

Variant links:

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]

YME1L1 links:

YME1L1 (HGNC:):

YME1L1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 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.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.827

PP5

Variant 10-27136371-G-A is Pathogenic according to our data. Variant chr10-27136371-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 374984.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr10-27136371-G-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
YME1L1	NM_014263.4 linkuse as main transcript	c.445C>T	p.Arg149Trp	missense_variant	5/19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3 linkuse as main transcript	c.616C>T	p.Arg206Trp	missense_variant	6/20		NP_647473.1
YME1L1	NM_001253866.2 linkuse as main transcript	c.346C>T	p.Arg116Trp	missense_variant	4/18		NP_001240795.1
YME1L1	XM_011519300.4 linkuse as main transcript	c.517C>T	p.Arg173Trp	missense_variant	5/19		XP_011517602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YME1L1	ENST00000376016.8 linkuse as main transcript	c.445C>T	p.Arg149Trp	missense_variant	5/19	1	NM_014263.4	ENSP00000365184.3		Q96TA2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250072

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135284

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460188

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Optic atrophy 11

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.46

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.67

.;D;.;T;T;.

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.92

LIST_S2

Pathogenic

0.99

D;D;D;D;D;D

M_CAP

Pathogenic

0.37

MetaRNN

Pathogenic

0.83

D;D;D;D;D;D

MetaSVM

Pathogenic

0.87

MutationAssessor

Benign

1.5

.;L;.;.;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-5.4

.;D;D;.;D;D

REVEL

Pathogenic

0.88

Sift

Pathogenic

0.0

.;D;D;.;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;.

Polyphen

1.0

.;D;D;.;.;.

Vest4

0.84

MutPred

0.59

.;Loss of solvent accessibility (P = 0.0036);.;Loss of solvent accessibility (P = 0.0036);.;.;

MVP

0.88

MPC

0.53

ClinPred

0.99

GERP RS

3.5

Varity_R

0.72

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over