rs325010

Variant names:

• chr6-44300181-A-G
• rs325010
• NM_020745.4:c.*366T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020745.4(AARS2):​c.*366T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.922 in 309,194 control chromosomes in the GnomAD database, including 133,211 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (60705 hom., cov: 31)
  • Exomes 𝑓: 0.96 (72506 hom.)
• Consequence: AARS2 NM_020745.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.55
• Publications: 4 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 6-44300181-A-G is Benign according to our data. Variant chr6-44300181-A-G is described in ClinVar as Benign. ClinVar VariationId is 357048.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.*366T>C		3_prime_UTR	Exon 22 of 22	NP_065796.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AARS2	ENST00000244571.5	TSL:1 MANE Select	c.*366T>C		3_prime_UTR	Exon 22 of 22	ENSP00000244571.4
	ENSG00000272442	ENST00000505802.1	TSL:2	n.313-6762A>G		intron	N/A	ENSP00000424257.1
	AARS2	ENST00000965666.1		c.*366T>C		3_prime_UTR	Exon 22 of 22	ENSP00000635725.1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134160 AN: 151582 Hom.: 60668 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.987

Gnomad AMR AF: 0.931

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.896

GnomAD4 exome AF: 0.958 AC: 150853 AN: 157494 Hom.: 72506 Cov.: 1 AF XY: 0.960 AC XY: 80652 AN XY: 84034

African (AFR) AF: 0.666 AC: 3386 AN: 5084

American (AMR) AF: 0.947 AC: 6904 AN: 7292

Ashkenazi Jewish (ASJ) AF: 0.924 AC: 3624 AN: 3924

East Asian (EAS) AF: 0.999 AC: 7449 AN: 7456

South Asian (SAS) AF: 0.965 AC: 26114 AN: 27054

European-Finnish (FIN) AF: 0.993 AC: 7263 AN: 7312

Middle Eastern (MID) AF: 0.890 AC: 548 AN: 616

European-Non Finnish (NFE) AF: 0.969 AC: 87860 AN: 90632

Other (OTH) AF: 0.948 AC: 7705 AN: 8124

GnomAD4 genome AF: 0.885 AC: 134248 AN: 151700 Hom.: 60705 Cov.: 31 AF XY: 0.887 AC XY: 65794 AN XY: 74170

African (AFR) AF: 0.675 AC: 27884 AN: 41312

American (AMR) AF: 0.931 AC: 14204 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3169 AN: 3456

East Asian (EAS) AF: 0.998 AC: 5158 AN: 5170

South Asian (SAS) AF: 0.961 AC: 4633 AN: 4820

European-Finnish (FIN) AF: 0.994 AC: 10511 AN: 10574

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

European-Non Finnish (NFE) AF: 0.968 AC: 65664 AN: 67806

Other (OTH) AF: 0.894 AC: 1882 AN: 2104

Alfa AF: 0.909 Hom.: 8261

Bravo AF: 0.871

Asia WGS AF: 0.938 AC: 3262 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Combined oxidative phosphorylation defect type 8 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.97
DANN	Benign	0.17
PhyloP100		-1.5
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: rs325010; hg19: chr6-44267918;