rs9833

Variant names:

• chr10-27111932-G-A
• rs9833
• NM_014263.4:c.*45C>T

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 2.02
• Publications: 18 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive optic atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• optic atrophy 11

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
YME1L1	NM_014263.4	c.*45C>T		3_prime_UTR_variant	Exon 19 of 19	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3	c.*45C>T		3_prime_UTR_variant	Exon 20 of 20		NP_647473.1
YME1L1	NM_001253866.2	c.*45C>T		3_prime_UTR_variant	Exon 18 of 18		NP_001240795.1
YME1L1	XM_011519300.4	c.*45C>T		3_prime_UTR_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.*45C>T		3_prime_UTR_variant	Exon 19 of 19	1	NM_014263.4	ENSP00000365184.3
YME1L1	ENST00000326799.7	c.*45C>T		3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000318480.3
YME1L1	ENST00000427324.6	c.*45C>T		3_prime_UTR_variant	Exon 18 of 18	3		ENSP00000398713.2
YME1L1	ENST00000491542.7	c.*45C>T		3_prime_UTR_variant	Exon 16 of 16	2		ENSP00000473557.2

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

GnomAD2 exomes AF: 0.848 AC: 212727 AN: 250992 AF XY: 0.849

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 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

African (AFR) AF: 0.897 AC: 29971 AN: 33426

American (AMR) AF: 0.735 AC: 32872 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 22121 AN: 26116

East Asian (EAS) AF: 0.985 AC: 39052 AN: 39644

South Asian (SAS) AF: 0.874 AC: 75360 AN: 86182

European-Finnish (FIN) AF: 0.926 AC: 48817 AN: 52736

Middle Eastern (MID) AF: 0.799 AC: 4597 AN: 5750

European-Non Finnish (NFE) AF: 0.822 AC: 911691 AN: 1109086

Other (OTH) AF: 0.841 AC: 50694 AN: 60296

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

African (AFR) AF: 0.897 AC: 37272 AN: 41542

American (AMR) AF: 0.775 AC: 11841 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.853 AC: 2957 AN: 3468

East Asian (EAS) AF: 0.990 AC: 5132 AN: 5186

South Asian (SAS) AF: 0.888 AC: 4283 AN: 4822

European-Finnish (FIN) AF: 0.932 AC: 9884 AN: 10608

Middle Eastern (MID) AF: 0.777 AC: 227 AN: 292

European-Non Finnish (NFE) AF: 0.825 AC: 56129 AN: 68012

Other (OTH) AF: 0.829 AC: 1752 AN: 2114

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Optic atrophy 11 Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9833; hg19: chr10-27400861;