10-27114599-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014263.4(YME1L1):c.1929T>C(p.Val643=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000515 in 1,611,258 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (3 hom.)
• Consequence: YME1L1 NM_014263.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.868

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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-27114599-A-G is Benign according to our data. Variant chr10-27114599-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 786152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-27114599-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.868 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
YME1L1	NM_014263.4	c.1929T>C	p.Val643=	synonymous_variant	18/19	ENST00000376016.8
YME1L1	NM_139312.3	c.2100T>C	p.Val700=	synonymous_variant	19/20
YME1L1	NM_001253866.2	c.1830T>C	p.Val610=	synonymous_variant	17/18
YME1L1	XM_011519300.4	c.2001T>C	p.Val667=	synonymous_variant	18/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
YME1L1	ENST00000376016.8	c.1929T>C	p.Val643=	synonymous_variant	18/19	1	NM_014263.4	P1
YME1L1	ENST00000326799.7	c.2100T>C	p.Val700=	synonymous_variant	19/20	1
YME1L1	ENST00000613434.4	c.1830T>C	p.Val610=	synonymous_variant	17/18	2

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 386 AN: 152170 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00879

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000788 AC: 195 AN: 247600 Hom.: 1 AF XY: 0.000598 AC XY: 80 AN XY: 133738

Gnomad AFR exome AF: 0.00926

Gnomad AMR exome AF: 0.000776

Gnomad ASJ exome AF: 0.000604

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000621

Gnomad OTH exome AF: 0.000498

GnomAD4 exome AF: 0.000302 AC: 440 AN: 1458970 Hom.: 3 Cov.: 30 AF XY: 0.000266 AC XY: 193 AN XY: 725616

Gnomad4 AFR exome AF: 0.00907

Gnomad4 AMR exome AF: 0.000842

Gnomad4 ASJ exome AF: 0.000614

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000820

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.000929

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152288 Hom.: 3 Cov.: 32 AF XY: 0.00258 AC XY: 192 AN XY: 74466

Gnomad4 AFR AF: 0.00883

Gnomad4 AMR AF: 0.000850

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00165 Hom.: 0

Bravo AF: 0.00293

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	YME1L1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	10
Dann	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs74128570; hg19: chr10-27403528;