NM_014263.4:c.1920+62C>A

Variant names:

• chr10-27115998-G-T
• rs2297151
• NM_014263.4:c.1920+62C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014263.4(YME1L1):​c.1920+62C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 1,410,214 control chromosomes in the GnomAD database, including 37,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4975 hom., cov: 31)
  • Exomes 𝑓: 0.21 (32535 hom.)
• Consequence: YME1L1 NM_014263.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0260
• Publications: 6 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
• optic atrophy 11

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-27115998-G-T is Benign according to our data. Variant chr10-27115998-G-T is described in ClinVar as Benign. ClinVar VariationId is 1294956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
YME1L1	NM_014263.4	c.1920+62C>A		intron_variant	Intron 17 of 18	ENST00000376016.8	NP_055078.1
YME1L1	NM_139312.3	c.2091+62C>A		intron_variant	Intron 18 of 19		NP_647473.1
YME1L1	NM_001253866.2	c.1821+62C>A		intron_variant	Intron 16 of 17		NP_001240795.1
YME1L1	XM_011519300.4	c.1992+62C>A		intron_variant	Intron 17 of 18		XP_011517602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
YME1L1	ENST00000376016.8	c.1920+62C>A		intron_variant	Intron 17 of 18	1	NM_014263.4	ENSP00000365184.3
YME1L1	ENST00000326799.7	c.2091+62C>A		intron_variant	Intron 18 of 19	1		ENSP00000318480.3
YME1L1	ENST00000427324.6	c.1821+62C>A		intron_variant	Intron 16 of 17	3		ENSP00000398713.2
YME1L1	ENST00000491542.7	c.1548+62C>A		intron_variant	Intron 14 of 15	2		ENSP00000473557.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36578 AN: 151844 Hom.: 4952 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: 0.562

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.224

GnomAD4 exome AF: 0.208 AC: 261384 AN: 1258252 Hom.: 32535 AF XY: 0.212 AC XY: 134194 AN XY: 634078

African (AFR) AF: 0.298 AC: 8432 AN: 28338

American (AMR) AF: 0.193 AC: 7575 AN: 39190

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5450 AN: 23954

East Asian (EAS) AF: 0.587 AC: 22687 AN: 38636

South Asian (SAS) AF: 0.364 AC: 28193 AN: 77536

European-Finnish (FIN) AF: 0.265 AC: 13983 AN: 52808

Middle Eastern (MID) AF: 0.212 AC: 790 AN: 3724

European-Non Finnish (NFE) AF: 0.172 AC: 162298 AN: 940934

Other (OTH) AF: 0.225 AC: 11976 AN: 53132

GnomAD4 genome AF: 0.241 AC: 36646 AN: 151962 Hom.: 4975 Cov.: 31 AF XY: 0.250 AC XY: 18579 AN XY: 74270

African (AFR) AF: 0.304 AC: 12586 AN: 41424

American (AMR) AF: 0.199 AC: 3049 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 758 AN: 3462

East Asian (EAS) AF: 0.563 AC: 2901 AN: 5152

South Asian (SAS) AF: 0.387 AC: 1860 AN: 4810

European-Finnish (FIN) AF: 0.271 AC: 2860 AN: 10564

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11927 AN: 67954

Other (OTH) AF: 0.234 AC: 493 AN: 2108

Alfa AF: 0.132 Hom.: 300

Bravo AF: 0.236

Asia WGS AF: 0.469 AC: 1629 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 16, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.34
PhyloP100		0.026
Mutation Taster		=100/0	polymorphism (auto)

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: rs2297151; hg19: chr10-27404927; COSMIC: COSV58760871;