chr10-27114599-A-G

Variant names:

• chr10-27114599-A-G
• rs74128570
• NM_014263.4:c.1929T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_014263.4(YME1L1):​c.1929T>C​(p.Val643Val) 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
• Publications: 1 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: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 786152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.868 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR,Unknown gene

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.1929T>C	p.Val643Val	synonymous	Exon 18 of 19	NP_055078.1	Q96TA2-2
	YME1L1	NM_139312.3		c.2100T>C	p.Val700Val	synonymous	Exon 19 of 20	NP_647473.1	Q96TA2-1
	YME1L1	NM_001253866.2		c.1830T>C	p.Val610Val	synonymous	Exon 17 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.1929T>C	p.Val643Val	synonymous	Exon 18 of 19	ENSP00000365184.3	Q96TA2-2
	YME1L1	ENST00000326799.7	TSL:1	c.2100T>C	p.Val700Val	synonymous	Exon 19 of 20	ENSP00000318480.3	Q96TA2-1
	YME1L1	ENST00000969517.1		c.2175T>C	p.Val725Val	synonymous	Exon 20 of 21	ENSP00000639576.1

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

GnomAD2 exomes AF: 0.000788 AC: 195 AN: 247600 AF XY: 0.000598

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 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

African (AFR) AF: 0.00907 AC: 302 AN: 33306

American (AMR) AF: 0.000842 AC: 37 AN: 43952

Ashkenazi Jewish (ASJ) AF: 0.000614 AC: 16 AN: 26042

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000820 AC: 7 AN: 85358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5756

European-Non Finnish (NFE) AF: 0.0000153 AC: 17 AN: 1111250

Other (OTH) AF: 0.000929 AC: 56 AN: 60290

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

African (AFR) AF: 0.00883 AC: 367 AN: 41546

American (AMR) AF: 0.000850 AC: 13 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.62
PhyloP100		0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=95/5	polymorphism

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: rs74128570; hg19: chr10-27403528;