rs2274636

Positions:

• chr10-27154083-A-G

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.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, single submitter B:1
• Conservation: PhyloP100: 0.00100

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=-0.8).
• 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_single_submitter, 1 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/exons	MANE	UniProt
YME1L1	NM_014263.4	c.33+95T>C		intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.33+95T>C		intron_variant
YME1L1	NM_139312.3	c.33+95T>C		intron_variant
YME1L1	XM_011519300.4	c.33+95T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.33+95T>C		intron_variant		1	NM_014263.4	P1

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

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.0898

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.114

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0970

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

Gnomad4 AFR AF: 0.0191

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0811

Gnomad4 OTH AF: 0.0990

Alfa AF: 0.0835 Hom.: 813

Bravo AF: 0.0741

Asia WGS AF: 0.237 AC: 823 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 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs2274636; hg19: chr10-27443012; COSMIC: COSV58762028; COSMIC: COSV58762028;