10-27114706-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.1921-99A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0912 in 802,560 control chromosomes in the GnomAD database, including 4,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (711 hom., cov: 32)
  • Exomes 𝑓: 0.093 (3873 hom.)
• Consequence: YME1L1 NM_014263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259

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=-0.91).
• BP6: Variant 10-27114706-T-C is Benign according to our data. Variant chr10-27114706-T-C is described in ClinVar as [Benign]. Clinvar id is 1279586.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.1921-99A>G		intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.1822-99A>G		intron_variant
YME1L1	NM_139312.3	c.2092-99A>G		intron_variant
YME1L1	XM_011519300.4	c.1993-99A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.1921-99A>G		intron_variant		1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2092-99A>G		intron_variant		1
YME1L1	ENST00000613434.4	c.1822-99A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12358 AN: 151916 Hom.: 699 Cov.: 32

Gnomad AFR AF: 0.0248

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0881

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0921

GnomAD4 exome AF: 0.0934 AC: 60784 AN: 650526 Hom.: 3873 AF XY: 0.0948 AC XY: 32404 AN XY: 341856

Gnomad4 AFR exome AF: 0.0221

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0902

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0761

Gnomad4 OTH exome AF: 0.0979

GnomAD4 genome AF: 0.0815 AC: 12391 AN: 152034 Hom.: 711 Cov.: 32 AF XY: 0.0880 AC XY: 6542 AN XY: 74300

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0881

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0832 Hom.: 601

Bravo AF: 0.0761

Asia WGS AF: 0.237 AC: 824 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	-0.91
Cadd	Benign	0.84
Dann	Benign	0.25

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: rs12782501; hg19: chr10-27403635; COSMIC: COSV58761631;