NM_014263.4:c.2008-7G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014263.4(YME1L1):c.2008-7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,606,350 control chromosomes in the GnomAD database, including 41,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4981 hom., cov: 31)

Exomes 𝑓: 0.21 ( 36235 hom. )

Consequence

YME1L1
NM_014263.4 splice_region, intron

Scores

Splicing: ADA: 0.00004169

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.705

Publications

13 publications found

Variant links:

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)

YME1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-27112127-C-T is Benign according to our data. Variant chr10-27112127-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
YME1L1	NM_014263.4	MANE Select	c.2008-7G>A	splice_region intron	N/A	NP_055078.1
YME1L1	NM_139312.3		c.2179-7G>A	splice_region intron	N/A	NP_647473.1
YME1L1	NM_001253866.2		c.1909-7G>A	splice_region intron	N/A	NP_001240795.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
YME1L1	ENST00000376016.8	TSL:1 MANE Select	c.2008-7G>A	splice_region intron	N/A	ENSP00000365184.3
YME1L1	ENST00000326799.7	TSL:1	c.2179-7G>A	splice_region intron	N/A	ENSP00000318480.3
YME1L1	ENST00000427324.6	TSL:3	c.1909-7G>A	splice_region intron	N/A	ENSP00000398713.2

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36586

AN:

151840

Hom.:

4958

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.177

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.563

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.176

Gnomad OTH

AF:

0.225

GnomAD2 exomes

AF:

0.250

AC:

61246

AN:

244922

AF XY:

0.252

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.559

Gnomad FIN exome

AF:

0.269

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.205

AC:

298488

AN:

1454390

Hom.:

36235

Cov.:

AF XY:

0.209

AC XY:

151203

AN XY:

723056

show subpopulations

African (AFR)

AF:

0.297

AC:

9833

AN:

33054

American (AMR)

AF:

0.193

AC:

8341

AN:

43262

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

5873

AN:

25888

East Asian (EAS)

AF:

0.587

AC:

23210

AN:

39554

South Asian (SAS)

AF:

0.363

AC:

30660

AN:

84550

European-Finnish (FIN)

AF:

0.264

AC:

14015

AN:

53068

Middle Eastern (MID)

AF:

0.210

AC:

1204

AN:

5722

European-Non Finnish (NFE)

AF:

0.173

AC:

191848

AN:

1109204

Other (OTH)

AF:

0.225

AC:

13504

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

10322

20644

30965

41287

51609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7204

14408

21612

28816

36020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.241

AC:

36654

AN:

151960

Hom.:

4981

Cov.:

AF XY:

0.250

AC XY:

18576

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.304

AC:

12586

AN:

41420

American (AMR)

AF:

0.199

AC:

3039

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

762

AN:

3472

East Asian (EAS)

AF:

0.564

AC:

2908

AN:

5158

South Asian (SAS)

AF:

0.386

AC:

1864

AN:

4826

European-Finnish (FIN)

AF:

0.270

AC:

2851

AN:

10558

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11941

AN:

67976

Other (OTH)

AF:

0.235

AC:

491

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1363

2726

4089

5452

6815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.197

Hom.:

1607

Bravo

AF:

0.236

Asia WGS

AF:

0.470

AC:

1633

AN:

3478

EpiCase

AF:

0.178

EpiControl

AF:

0.178

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

May 05, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.86

(source)

DANN

Benign

0.56

PhyloP100

-0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.010

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over