rs2274636

Variant names:

• chr10-27154083-A-G
• rs2274636
• NM_014263.4:c.33+95T>C

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.33+95T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0873 in 1,459,326 control chromosomes in the GnomAD database, including 7,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (704 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6444 hom.)
• Consequence: YME1L1 NM_014263.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00100
• Publications: 9 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=-0.8).
• BP6: Variant 10-27154083-A-G is Benign according to our data. Variant chr10-27154083-A-G is described in ClinVar as [Benign]. Clinvar id is 1251578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YME1L1	NM_014263.4	c.33+95T>C		intron_variant	Intron 1 of 18	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3	c.33+95T>C		intron_variant	Intron 1 of 19		NP_647473.1
YME1L1	NM_001253866.2	c.33+95T>C		intron_variant	Intron 1 of 17		NP_001240795.1
YME1L1	XM_011519300.4	c.33+95T>C		intron_variant	Intron 1 of 18		XP_011517602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YME1L1	ENST00000376016.8	c.33+95T>C		intron_variant	Intron 1 of 18	1	NM_014263.4	ENSP00000365184.3

Frequencies

GnomAD3 genomes AF: 0.0797 AC: 12120 AN: 152100 Hom.: 692 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.0505

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0890

GnomAD4 exome AF: 0.0882 AC: 115323 AN: 1307108 Hom.: 6444 AF XY: 0.0895 AC XY: 58119 AN XY: 649398

African (AFR) AF: 0.0151 AC: 449 AN: 29670

American (AMR) AF: 0.110 AC: 3892 AN: 35272

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 2185 AN: 24336

East Asian (EAS) AF: 0.275 AC: 9678 AN: 35256

South Asian (SAS) AF: 0.136 AC: 10506 AN: 77006

European-Finnish (FIN) AF: 0.114 AC: 5591 AN: 49168

Middle Eastern (MID) AF: 0.0913 AC: 503 AN: 5508

European-Non Finnish (NFE) AF: 0.0775 AC: 77208 AN: 996112

Other (OTH) AF: 0.0970 AC: 5311 AN: 54780

GnomAD4 genome AF: 0.0798 AC: 12147 AN: 152218 Hom.: 704 Cov.: 32 AF XY: 0.0864 AC XY: 6432 AN XY: 74406

African (AFR) AF: 0.0191 AC: 795 AN: 41548

American (AMR) AF: 0.111 AC: 1694 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1474 AN: 5170

South Asian (SAS) AF: 0.151 AC: 728 AN: 4824

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10588

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.0811 AC: 5518 AN: 68016

Other (OTH) AF: 0.0990 AC: 209 AN: 2112

Alfa AF: 0.0822 Hom.: 1169

Bravo AF: 0.0741

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.52
PhyloP100		0.0010
PromoterAI		0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2274636; hg19: chr10-27443012; COSMIC: COSV58762028; COSMIC: COSV58762028;