Genetic Variant YME1L1:c.1920+62C>A (chr10-27115998-G-T) – ACMG Classification: Benign (-20 pts)

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.1920+62C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,410,214 control chromosomes in the GnomAD database, including 37,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4975 hom., cov: 31)

Exomes 𝑓: 0.21 ( 32535 hom. )

Consequence

YME1L1
NM_014263.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0260

Publications

6 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
mitochondrial disease
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
optic atrophy 11
Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, 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=-0.9).

BP6

Variant 10-27115998-G-T is Benign according to our data. Variant chr10-27115998-G-T is described in ClinVar as Benign. ClinVar VariationId is 1294956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 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	UniProt
YME1L1	NM_014263.4	MANE Select	c.1920+62C>A	intron	N/A	NP_055078.1	Q96TA2-2
YME1L1	NM_139312.3		c.2091+62C>A	intron	N/A	NP_647473.1	Q96TA2-1
YME1L1	NM_001253866.2		c.1821+62C>A	intron	N/A	NP_001240795.1	Q96TA2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YME1L1	ENST00000376016.8	TSL:1 MANE Select	c.1920+62C>A	intron	N/A	ENSP00000365184.3	Q96TA2-2
YME1L1	ENST00000326799.7	TSL:1	c.2091+62C>A	intron	N/A	ENSP00000318480.3	Q96TA2-1
YME1L1	ENST00000969517.1		c.2166+62C>A	intron	N/A	ENSP00000639576.1

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36578

AN:

151844

Hom.:

4952

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:

0.562

Gnomad SAS

AF:

0.388

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.224

GnomAD4 exome

AF:

0.208

AC:

261384

AN:

1258252

Hom.:

32535

AF XY:

0.212

AC XY:

134194

AN XY:

634078

show subpopulations

African (AFR)

AF:

0.298

AC:

8432

AN:

28338

American (AMR)

AF:

0.193

AC:

7575

AN:

39190

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

5450

AN:

23954

East Asian (EAS)

AF:

0.587

AC:

22687

AN:

38636

South Asian (SAS)

AF:

0.364

AC:

28193

AN:

77536

European-Finnish (FIN)

AF:

0.265

AC:

13983

AN:

52808

Middle Eastern (MID)

AF:

0.212

AC:

790

AN:

3724

European-Non Finnish (NFE)

AF:

0.172

AC:

162298

AN:

940934

Other (OTH)

AF:

0.225

AC:

11976

AN:

53132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

9744

19489

29233

38978

48722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5714

11428

17142

22856

28570

<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:

36646

AN:

151962

Hom.:

4975

Cov.:

AF XY:

0.250

AC XY:

18579

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.304

AC:

12586

AN:

41424

American (AMR)

AF:

0.199

AC:

3049

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

758

AN:

3462

East Asian (EAS)

AF:

0.563

AC:

2901

AN:

5152

South Asian (SAS)

AF:

0.387

AC:

1860

AN:

4810

European-Finnish (FIN)

AF:

0.271

AC:

2860

AN:

10564

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11927

AN:

67954

Other (OTH)

AF:

0.234

AC:

493

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1363

2726

4090

5453

6816

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:

0.132

Hom.:

300

Bravo

AF:

0.236

Asia WGS

AF:

0.469

AC:

1629

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

8.1

(source)

DANN

Benign

0.34

PhyloP100

0.026

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

Computational scores

Splicing

Publications

Other links and lift over