10-27114329-T-A

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.2007+192A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 152,276 control chromosomes in the GnomAD database, including 246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.054 (246 hom., cov: 32)
• Consequence: YME1L1 NM_014263.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.949

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=-0.79).
• BP6: Variant 10-27114329-T-A is Benign according to our data. Variant chr10-27114329-T-A is described in ClinVar as [Benign]. Clinvar id is 1263309.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.2007+192A>T		intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.1908+192A>T		intron_variant
YME1L1	NM_139312.3	c.2178+192A>T		intron_variant
YME1L1	XM_011519300.4	c.2079+192A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.2007+192A>T		intron_variant		1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2178+192A>T		intron_variant		1
YME1L1	ENST00000613434.4	c.1908+192A>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0544 AC: 8281 AN: 152158 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0706

Gnomad EAS AF: 0.00307

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0430

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0544 AC: 8290 AN: 152276 Hom.: 246 Cov.: 32 AF XY: 0.0535 AC XY: 3982 AN XY: 74460

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.0322

Gnomad4 ASJ AF: 0.0706

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0518

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0425

Alfa AF: 0.0602 Hom.: 38

Bravo AF: 0.0544

Asia WGS AF: 0.0340 AC: 118 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 24, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	8.4
Dann	Benign	0.81

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: rs73598021; hg19: chr10-27403258;