10-27111990-A-G

Variant names:

• chr10-27111990-A-G
• NM_014263.4:c.2138T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014263.4(YME1L1):​c.2138T>C​(p.Leu713Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: YME1L1 NM_014263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.29
• Publications: 0 publications found

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]

YME1L1 Gene-Disease associations (from GenCC):

• autosomal recessive optic atrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• mitochondrial disease

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• optic atrophy 11

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014263.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YME1L1	NM_014263.4	MANE Select	c.2138T>C	p.Leu713Ser	missense	Exon 19 of 19	NP_055078.1	Q96TA2-2
	YME1L1	NM_139312.3		c.2309T>C	p.Leu770Ser	missense	Exon 20 of 20	NP_647473.1	Q96TA2-1
	YME1L1	NM_001253866.2		c.2039T>C	p.Leu680Ser	missense	Exon 18 of 18	NP_001240795.1	Q96TA2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YME1L1	ENST00000376016.8	TSL:1 MANE Select	c.2138T>C	p.Leu713Ser	missense	Exon 19 of 19	ENSP00000365184.3	Q96TA2-2
	YME1L1	ENST00000326799.7	TSL:1	c.2309T>C	p.Leu770Ser	missense	Exon 20 of 20	ENSP00000318480.3	Q96TA2-1
	YME1L1	ENST00000969517.1		c.2384T>C	p.Leu795Ser	missense	Exon 21 of 21	ENSP00000639576.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.43
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.28	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Uncertain	0.0039	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		9.3
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-3.1	D
REVEL	Pathogenic	0.84
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.38		Gain of phosphorylation at L770 (P = 0.0252)
MVP		0.51
MPC		2.2
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.40
gMVP		0.69
Mutation Taster		=34/66	disease causing

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

Other links and lift over

hg19: chr10-27400919;