10-27112098-T-A

Variant names:

• chr10-27112098-T-A
• rs142481948
• NM_014263.4:c.2030A>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1 PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.98

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.

• 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	UniProt
YME1L1	NM_014263.4	c.2030A>T	p.His677Leu	missense_variant	Exon 19 of 19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3	c.2201A>T	p.His734Leu	missense_variant	Exon 20 of 20		NP_647473.1
YME1L1	NM_001253866.2	c.1931A>T	p.His644Leu	missense_variant	Exon 18 of 18		NP_001240795.1
YME1L1	XM_011519300.4	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	Appris	UniProt
YME1L1	ENST00000376016.8	c.2030A>T	p.His677Leu	missense_variant	Exon 19 of 19	1	NM_014263.4	ENSP00000365184.3
YME1L1	ENST00000326799.7	c.2201A>T	p.His734Leu	missense_variant	Exon 20 of 20	1		ENSP00000318480.3
YME1L1	ENST00000613434.4	c.1931A>T	p.His644Leu	missense_variant	Exon 18 of 18	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250918 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135588

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: 31 AN: 1461470 Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13 AN XY: 727020

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.: 32

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00000824 AC: 1

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	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.25	.;T;.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.13	T;T;T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	0.24	.;N;.;.
PrimateAI	Uncertain	0.60	T
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	T
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

Other links and lift over

dbSNP: rs142481948; hg19: chr10-27401027;