Variant 10-27112008-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong

The NM_014263.4(YME1L1):c.2120T>G(p.Val707Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

YME1L1
NM_014263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.29

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 Likely_pathogenic. Variant got 7 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, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
YME1L1	NM_014263.4 linkuse as main transcript	c.2120T>G	p.Val707Gly	missense_variant	19/19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3 linkuse as main transcript	c.2291T>G	p.Val764Gly	missense_variant	20/20		NP_647473.1
YME1L1	NM_001253866.2 linkuse as main transcript	c.2021T>G	p.Val674Gly	missense_variant	18/18		NP_001240795.1
YME1L1	XM_011519300.4 linkuse as main transcript	c.2192T>G	p.Val731Gly	missense_variant	19/19		XP_011517602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YME1L1	ENST00000376016.8 linkuse as main transcript	c.2120T>G	p.Val707Gly	missense_variant	19/19	1	NM_014263.4	ENSP00000365184.3	Q96TA2-2
YME1L1	ENST00000326799.7 linkuse as main transcript	c.2291T>G	p.Val764Gly	missense_variant	20/20	1		ENSP00000318480.3	Q96TA2-1
YME1L1	ENST00000613434.4 linkuse as main transcript	c.2021T>G	p.Val674Gly	missense_variant	18/18	2			Q96TA2-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.2291T>G (p.V764G) alteration is located in exon 20 (coding exon 20) of the YME1L1 gene. This alteration results from a T to G substitution at nucleotide position 2291, causing the valine (V) at amino acid position 764 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.71

.;D;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.82

T;T;T

M_CAP

Pathogenic

0.52

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Uncertain

0.73

MutationAssessor

Uncertain

2.8

.;M;.

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-6.4

.;D;D

REVEL

Pathogenic

0.91

Sift

Pathogenic

0.0

.;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

0.99, 0.97

.;D;D

Vest4

0.70

MutPred

0.85

.;Loss of stability (P = 0.005);.;

MVP

0.85

MPC

2.1

ClinPred

1.0

GERP RS

5.5

Varity_R

0.82

gMVP

0.82

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

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