10-27114751-G-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.1921-144C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 567,410 control chromosomes in the GnomAD database, including 1,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.076 (642 hom., cov: 32)
  • Exomes 𝑓: 0.051 (783 hom.)
• Consequence: YME1L1 NM_014263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.282

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=-0.99).
• BP6: Variant 10-27114751-G-C is Benign according to our data. Variant chr10-27114751-G-C is described in ClinVar as [Benign]. Clinvar id is 1257417.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.1921-144C>G		intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.1822-144C>G		intron_variant
YME1L1	NM_139312.3	c.2092-144C>G		intron_variant
YME1L1	XM_011519300.4	c.1993-144C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.1921-144C>G		intron_variant		1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2092-144C>G		intron_variant		1
YME1L1	ENST00000613434.4	c.1822-144C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0757 AC: 11512 AN: 152078 Hom.: 645 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0332

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0714

GnomAD4 exome AF: 0.0513 AC: 21315 AN: 415214 Hom.: 783 AF XY: 0.0525 AC XY: 11480 AN XY: 218558

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0275

Gnomad4 ASJ exome AF: 0.0563

Gnomad4 EAS exome AF: 0.101

Gnomad4 SAS exome AF: 0.0864

Gnomad4 FIN exome AF: 0.0438

Gnomad4 NFE exome AF: 0.0399

Gnomad4 OTH exome AF: 0.0579

GnomAD4 genome AF: 0.0756 AC: 11512 AN: 152196 Hom.: 642 Cov.: 32 AF XY: 0.0743 AC XY: 5530 AN XY: 74410

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.0330

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.0793

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0401

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0213 Hom.: 7

Bravo AF: 0.0793

Asia WGS AF: 0.0770 AC: 266 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.90
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: rs10829187; hg19: chr10-27403680;