NM_020745.4:c.*1635_*1636insAA

Variant names:

• chr6-44298911-C-CTT
• rs34687863
• NM_020745.4:c.*1635_*1636insAA

Variant summary

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

The NM_020745.4(AARS2):​c.*1635_*1636insAA 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 (60972 hom., cov: 0)
• Consequence: AARS2 NM_020745.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.134
• Publications: 2 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 6-44298911-C-CTT is Benign according to our data. Variant chr6-44298911-C-CTT is described in ClinVar as Benign. ClinVar VariationId is 357026.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: NM_020745.4. 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
	AARS2	NM_020745.4	MANE Select	c.*1635_*1636insAA		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.*1635_*1636insAA		3_prime_UTR	Exon 22 of 22	ENSP00000244571.4	Q5JTZ9
	ENSG00000272442	ENST00000505802.1	TSL:2	n.313-8031_313-8030insTT		intron	N/A	ENSP00000424257.1	H0Y9J4
	AARS2	ENST00000932746.1		c.*1635_*1636insAA		3_prime_UTR	Exon 21 of 21	ENSP00000602805.1

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134610 AN: 151956 Hom.: 60935 Cov.: 0

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.988

Gnomad AMR AF: 0.932

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.898

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

GnomAD4 genome AF: 0.886 AC: 134698 AN: 152074 Hom.: 60972 Cov.: 0 AF XY: 0.888 AC XY: 66028 AN XY: 74356

African (AFR) AF: 0.676 AC: 27975 AN: 41408

American (AMR) AF: 0.932 AC: 14246 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3205 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5148 AN: 5158

South Asian (SAS) AF: 0.962 AC: 4633 AN: 4818

European-Finnish (FIN) AF: 0.995 AC: 10557 AN: 10612

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

European-Non Finnish (NFE) AF: 0.969 AC: 65898 AN: 68002

Other (OTH) AF: 0.896 AC: 1892 AN: 2112

Alfa AF: 0.916 Hom.: 7867

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		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34687863; hg19: chr6-44266648; COSMIC: COSV55113072; COSMIC: COSV55113072;