NM_014263.4:c.2030A>G

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong

The NM_014263.4(YME1L1):c.2030A>G(p.His677Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

YME1L1
NM_014263.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM1

In a binding_site (size 0) in uniprot entity YMEL1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06675786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
YME1L1	NM_014263.4 link	c.2030A>G	p.His677Arg	missense_variant	Exon 19 of 19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3 link	c.2201A>G	p.His734Arg	missense_variant	Exon 20 of 20		NP_647473.1
YME1L1	NM_001253866.2 link	c.1931A>G	p.His644Arg	missense_variant	Exon 18 of 18		NP_001240795.1
YME1L1	XM_011519300.4 link	c.2102A>G	p.His701Arg	missense_variant	Exon 19 of 19		XP_011517602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
YME1L1	ENST00000376016.8 link	c.2030A>G	p.His677Arg	missense_variant	Exon 19 of 19	1	NM_014263.4	ENSP00000365184.3	Q96TA2-2
YME1L1	ENST00000326799.7 link	c.2201A>G	p.His734Arg	missense_variant	Exon 20 of 20	1		ENSP00000318480.3	Q96TA2-1
YME1L1	ENST00000613434.4 link	c.1931A>G	p.His644Arg	missense_variant	Exon 18 of 18	2			Q96TA2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250918

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461470

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727020

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 16, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬¨‚Ä† is likely to be tolerated. This variant has not been reported in the literature in individuals affected with YME1L1-related conditions. This variant is present in population databases (rs142481948, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 734 of the YME1L1 protein (p.His734Arg). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.14

.;T;.;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.38

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.97

D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.067

T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Benign

-0.85

.;N;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.58

.;N;N;.

REVEL

Benign

0.21

Sift

Benign

0.54

.;T;T;.

Sift4G

Benign

0.52

T;T;T;T

Polyphen

0.021, 0.0

.;B;B;.

Vest4

0.28

MutPred

0.34

.;Gain of MoRF binding (P = 0.0183);.;Gain of MoRF binding (P = 0.0183);

MVP

0.41

MPC

1.0

ClinPred

0.036

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.42

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