10-27111932-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014263.4(YME1L1):c.*45C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 1,610,184 control chromosomes in the GnomAD database, including 563,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (55993 hom., cov: 32)
  • Exomes 𝑓: 0.83 (507835 hom.)
• Consequence: YME1L1 NM_014263.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.02

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-27111932-G-A is Benign according to our data. Variant chr10-27111932-G-A is described in ClinVar as [Benign]. Clinvar id is 1259033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.*45C>T		3_prime_UTR_variant	19/19	ENST00000376016.8
YME1L1	NM_001253866.2	c.*45C>T		3_prime_UTR_variant	18/18
YME1L1	NM_139312.3	c.*45C>T		3_prime_UTR_variant	20/20
YME1L1	XM_011519300.4	c.*45C>T		3_prime_UTR_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.*45C>T		3_prime_UTR_variant	19/19	1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.*45C>T		3_prime_UTR_variant	20/20	1
YME1L1	ENST00000613434.4	c.*45C>T		3_prime_UTR_variant	18/18	2

Frequencies

GnomAD3 genomes AF: 0.855 AC: 130115 AN: 152116 Hom.: 55954 Cov.: 32

Gnomad AFR AF: 0.897

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.776

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.932

Gnomad MID AF: 0.780

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.827

GnomAD3 exomes AF: 0.848 AC: 212727 AN: 250992 Hom.: 90741 AF XY: 0.849 AC XY: 115270 AN XY: 135698

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.847

Gnomad EAS exome AF: 0.992

Gnomad SAS exome AF: 0.879

Gnomad FIN exome AF: 0.932

Gnomad NFE exome AF: 0.828

Gnomad OTH exome AF: 0.833

GnomAD4 exome AF: 0.833 AC: 1215175 AN: 1457950 Hom.: 507835 Cov.: 32 AF XY: 0.835 AC XY: 605624 AN XY: 725532

Gnomad4 AFR exome AF: 0.897

Gnomad4 AMR exome AF: 0.735

Gnomad4 ASJ exome AF: 0.847

Gnomad4 EAS exome AF: 0.985

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.926

Gnomad4 NFE exome AF: 0.822

Gnomad4 OTH exome AF: 0.841

GnomAD4 genome AF: 0.855 AC: 130205 AN: 152234 Hom.: 55993 Cov.: 32 AF XY: 0.863 AC XY: 64264 AN XY: 74446

Gnomad4 AFR AF: 0.897

Gnomad4 AMR AF: 0.775

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.888

Gnomad4 FIN AF: 0.932

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.829

Alfa AF: 0.834 Hom.: 13910

Bravo AF: 0.844

Asia WGS AF: 0.932 AC: 3241 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Optic atrophy 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	13
Dann	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9833; hg19: chr10-27400861;