10-27112127-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014263.4(YME1L1):c.2008-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,606,350 control chromosomes in the GnomAD database, including 41,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4981 hom., cov: 31)
  • Exomes 𝑓: 0.21 (36235 hom.)
• Consequence: YME1L1 NM_014263.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00004169
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.705

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-27112127-C-T is Benign according to our data. Variant chr10-27112127-C-T is described in ClinVar as [Benign]. Clinvar id is 1277257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.2008-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000376016.8
YME1L1	NM_001253866.2	c.1909-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
YME1L1	NM_139312.3	c.2179-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
YME1L1	XM_011519300.4	c.2080-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.2008-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2179-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
YME1L1	ENST00000613434.4	c.1909-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36586 AN: 151840 Hom.: 4958 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: 0.563

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.225

GnomAD3 exomes AF: 0.250 AC: 61246 AN: 244922 Hom.: 9153 AF XY: 0.252 AC XY: 33321 AN XY: 132260

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.196

Gnomad ASJ exome AF: 0.229

Gnomad EAS exome AF: 0.559

Gnomad SAS exome AF: 0.371

Gnomad FIN exome AF: 0.269

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.205 AC: 298488 AN: 1454390 Hom.: 36235 Cov.: 34 AF XY: 0.209 AC XY: 151203 AN XY: 723056

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.193

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.587

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.264

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.241 AC: 36654 AN: 151960 Hom.: 4981 Cov.: 31 AF XY: 0.250 AC XY: 18576 AN XY: 74272

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.235

Alfa AF: 0.196 Hom.: 1568

Bravo AF: 0.236

Asia WGS AF: 0.470 AC: 1633 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.178

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Optic atrophy 11 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.86
Dann	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000042
dbscSNV1_RF	Benign	0.010
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: rs11015538; hg19: chr10-27401056; COSMIC: COSV58758389;