10-27115998-G-T

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.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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0260

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=-0.9).
• BP6: Variant 10-27115998-G-T is Benign according to our data. Variant chr10-27115998-G-T is described in ClinVar as [Benign]. Clinvar id is 1294956.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.1920+62C>A		intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.1821+62C>A		intron_variant
YME1L1	NM_139312.3	c.2091+62C>A		intron_variant
YME1L1	XM_011519300.4	c.1992+62C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.1920+62C>A		intron_variant		1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2091+62C>A		intron_variant		1
YME1L1	ENST00000613434.4	c.1821+62C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36578 AN: 151844 Hom.: 4952 Cov.: 31

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

Gnomad4 AFR exome AF: 0.298

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.364

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.241 AC: 36646 AN: 151962 Hom.: 4975 Cov.: 31 AF XY: 0.250 AC XY: 18579 AN XY: 74270

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.234

Alfa AF: 0.132 Hom.: 300

Bravo AF: 0.236

Asia WGS AF: 0.469 AC: 1629 AN: 3476

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	8.1
Dann	Benign	0.34

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: rs2297151; hg19: chr10-27404927; COSMIC: COSV58760871;