rs117297789

Variant names:

• chr10-27112157-T-C
• rs117297789
• NM_014263.4:c.2008-37A>G

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.2008-37A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00573 in 1,572,602 control chromosomes in the GnomAD database, including 322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (41 hom., cov: 31)
  • Exomes 𝑓: 0.0057 (281 hom.)
• Consequence: YME1L1 NM_014263.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.76
• Publications: 1 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
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• optic atrophy 11

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-27112157-T-C is Benign according to our data. Variant chr10-27112157-T-C is described in ClinVar as Benign. ClinVar VariationId is 1269537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YME1L1	NM_014263.4	MANE Select	c.2008-37A>G		intron	N/A	NP_055078.1	Q96TA2-2
	YME1L1	NM_139312.3		c.2179-37A>G		intron	N/A	NP_647473.1	Q96TA2-1
	YME1L1	NM_001253866.2		c.1909-37A>G		intron	N/A	NP_001240795.1	Q96TA2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YME1L1	ENST00000376016.8	TSL:1 MANE Select	c.2008-37A>G		intron	N/A	ENSP00000365184.3	Q96TA2-2
	YME1L1	ENST00000326799.7	TSL:1	c.2179-37A>G		intron	N/A	ENSP00000318480.3	Q96TA2-1
	YME1L1	ENST00000969517.1		c.2254-37A>G		intron	N/A	ENSP00000639576.1

Frequencies

GnomAD3 genomes AF: 0.00604 AC: 919 AN: 152156 Hom.: 41 Cov.: 31

Gnomad AFR AF: 0.000796

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0240

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.00957

GnomAD2 exomes AF: 0.0125 AC: 2787 AN: 223082 AF XY: 0.0125

Gnomad AFR exome AF: 0.000949

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.000494

Gnomad EAS exome AF: 0.118

Gnomad FIN exome AF: 0.00169

Gnomad NFE exome AF: 0.00184

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00570 AC: 8089 AN: 1420328 Hom.: 281 Cov.: 31 AF XY: 0.00606 AC XY: 4263 AN XY: 702938

African (AFR) AF: 0.00149 AC: 47 AN: 31534

American (AMR) AF: 0.00113 AC: 41 AN: 36342

Ashkenazi Jewish (ASJ) AF: 0.000780 AC: 19 AN: 24374

East Asian (EAS) AF: 0.105 AC: 4099 AN: 39100

South Asian (SAS) AF: 0.0189 AC: 1517 AN: 80122

European-Finnish (FIN) AF: 0.00228 AC: 118 AN: 51772

Middle Eastern (MID) AF: 0.00288 AC: 16 AN: 5546

European-Non Finnish (NFE) AF: 0.00152 AC: 1663 AN: 1093008

Other (OTH) AF: 0.00972 AC: 569 AN: 58530

GnomAD4 genome AF: 0.00604 AC: 919 AN: 152274 Hom.: 41 Cov.: 31 AF XY: 0.00698 AC XY: 520 AN XY: 74446

African (AFR) AF: 0.000794 AC: 33 AN: 41558

American (AMR) AF: 0.00177 AC: 27 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.116 AC: 602 AN: 5188

South Asian (SAS) AF: 0.0238 AC: 115 AN: 4828

European-Finnish (FIN) AF: 0.00132 AC: 14 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 68010

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00281 Hom.: 0

Bravo AF: 0.00646

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.38
PhyloP100		-1.8
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: rs117297789; hg19: chr10-27401086; COSMIC: COSV58760865;