10-27112157-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: -1.76

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1269537.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.2008-37A>G		intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.1909-37A>G		intron_variant
YME1L1	NM_139312.3	c.2179-37A>G		intron_variant
YME1L1	XM_011519300.4	c.2080-37A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.2008-37A>G		intron_variant		1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2179-37A>G		intron_variant		1
YME1L1	ENST00000613434.4	c.1909-37A>G		intron_variant		2

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

GnomAD3 exomes AF: 0.0125 AC: 2787 AN: 223082 Hom.: 121 AF XY: 0.0125 AC XY: 1511 AN XY: 120752

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 SAS exome AF: 0.0186

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

Gnomad4 AFR exome AF: 0.00149

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.000780

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.00228

Gnomad4 NFE exome AF: 0.00152

Gnomad4 OTH exome AF: 0.00972

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

Gnomad4 AFR AF: 0.000794

Gnomad4 AMR AF: 0.00177

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0238

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00154

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00281 Hom.: 0

Bravo AF: 0.00646

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 17, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.4
Dann	Benign	0.38

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

LitVar

Other links and lift over

dbSNP: rs117297789; hg19: chr10-27401086; COSMIC: COSV58760865;