ENST00000244571:c.*1284delA

Variant names:

• chr6-44299262-CT-C
• rs35562884
• NM_020745.4:c.*1284delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000244571.5(AARS2):​c.*1284delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.89 (60554 hom., cov: 0)
• Consequence: AARS2 ENST00000244571.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.885
• Publications: 1 publications found

Genes affected

AARS2 (HGNC:21022): (alanyl-tRNA synthetase 2, mitochondrial) The protein encoded by this gene belongs to the class-II aminoacyl-tRNA synthetase family. Aminoacyl-tRNA synthetases play critical roles in mRNA translation by charging tRNAs with their cognate amino acids. The encoded protein is a mitochondrial enzyme that specifically aminoacylates alanyl-tRNA. Mutations in this gene are a cause of combined oxidative phosphorylation deficiency 8. [provided by RefSeq, Dec 2011]

ENSG00000272442 (HGNC:):

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-44299262-CT-C is Benign according to our data. Variant chr6-44299262-CT-C is described in ClinVar as Benign. ClinVar VariationId is 357035.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000244571.5. 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
	AARS2	NM_020745.4	MANE Select	c.*1284delA		3_prime_UTR	Exon 22 of 22	NP_065796.2	Q5JTZ9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AARS2	ENST00000244571.5	TSL:1 MANE Select	c.*1284delA		3_prime_UTR	Exon 22 of 22	ENSP00000244571.4	Q5JTZ9
	ENSG00000272442	ENST00000505802.1	TSL:2	n.313-7673delT		intron	N/A	ENSP00000424257.1	H0Y9J4
	AARS2	ENST00000932746.1		c.*1284delA		3_prime_UTR	Exon 21 of 21	ENSP00000602805.1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 133855 AN: 150692 Hom.: 60514 Cov.: 0

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.962

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.902

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.888 AC: 133948 AN: 150808 Hom.: 60554 Cov.: 0 AF XY: 0.890 AC XY: 65589 AN XY: 73668

African (AFR) AF: 0.682 AC: 27661 AN: 40588

American (AMR) AF: 0.930 AC: 14127 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3196 AN: 3462

East Asian (EAS) AF: 0.998 AC: 5051 AN: 5060

South Asian (SAS) AF: 0.962 AC: 4611 AN: 4794

European-Finnish (FIN) AF: 0.995 AC: 10410 AN: 10464

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65863 AN: 67956

Other (OTH) AF: 0.900 AC: 1885 AN: 2094

Alfa AF: 0.928 Hom.: 3166

Bravo AF: 0.869

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Combined oxidative phosphorylation deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.89
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: rs35562884; hg19: chr6-44266999;