dbSNP rs142481948: YME1L1:p.His677Leu (chr10-27112098-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_014263.4(YME1L1):c.2030A>T(p.His677Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000212 in 1,461,470 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 0.000021 ( 0 hom. )

Consequence

YME1L1
NM_014263.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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 2 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=0.1314731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
YME1L1	NM_014263.4 link	c.2030A>T	p.His677Leu	missense_variant	Exon 19 of 19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3 link	c.2201A>T	p.His734Leu	missense_variant	Exon 20 of 20		NP_647473.1
YME1L1	NM_001253866.2 link	c.1931A>T	p.His644Leu	missense_variant	Exon 18 of 18		NP_001240795.1
YME1L1	XM_011519300.4 link	c.2102A>T	p.His701Leu	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>T	p.His677Leu	missense_variant	Exon 19 of 19	1	NM_014263.4	ENSP00000365184.3	Q96TA2-2
YME1L1	ENST00000326799.7 link	c.2201A>T	p.His734Leu	missense_variant	Exon 20 of 20	1		ENSP00000318480.3	Q96TA2-1
YME1L1	ENST00000613434.4 link	c.1931A>T	p.His644Leu	missense_variant	Exon 18 of 18	2			Q96TA2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000797

AC:

AN:

250918

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135588

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000212

AC:

AN:

1461470

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727020

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:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Uncertain

0.026

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.25

.;T;.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.18

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-0.31

MutationAssessor

Benign

0.24

.;N;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.1

.;N;N;.

REVEL

Benign

0.27

Sift

Benign

0.30

.;T;T;.

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.0040, 0.0010

.;B;B;.

Vest4

0.35

MVP

0.38

MPC

1.1

ClinPred

0.23

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.59

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over