10-27112082-A-G

Variant names:

• chr10-27112082-A-G
• rs751557810
• NM_014263.4:c.2046T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014263.4(YME1L1):​c.2046T>C​(p.His682His) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000137 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: YME1L1 NM_014263.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.75
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 10-27112082-A-G is Benign according to our data. Variant chr10-27112082-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1903850.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2046T>C	p.His682His	synonymous	Exon 19 of 19	NP_055078.1	Q96TA2-2
	YME1L1	NM_139312.3		c.2217T>C	p.His739His	synonymous	Exon 20 of 20	NP_647473.1	Q96TA2-1
	YME1L1	NM_001253866.2		c.1947T>C	p.His649His	synonymous	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.2046T>C	p.His682His	synonymous	Exon 19 of 19	ENSP00000365184.3	Q96TA2-2
	YME1L1	ENST00000326799.7	TSL:1	c.2217T>C	p.His739His	synonymous	Exon 20 of 20	ENSP00000318480.3	Q96TA2-1
	YME1L1	ENST00000969517.1		c.2292T>C	p.His764His	synonymous	Exon 21 of 21	ENSP00000639576.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251278 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461696 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727132

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86230

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111960

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	6.3
DANN	Benign	0.38
PhyloP100		3.8
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

Other links and lift over

dbSNP: rs751557810; hg19: chr10-27401011;