6-44298911-C-CTT

Variant summary

Our verdict is Benign. Variant got -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

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]

POLR1C (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AARS2	NM_020745.4	c.*1635_*1636insAA		3_prime_UTR_variant	22/22	ENST00000244571.5
AARS2	XM_005249245.4	c.*1635_*1636insAA		3_prime_UTR_variant	20/20
POLR1C	NM_001318876.2	c.946-142978_946-142977insTT		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AARS2	ENST00000244571.5	c.*1635_*1636insAA		3_prime_UTR_variant	22/22	1	NM_020745.4	P1
TMEM151B	ENST00000438774.2	c.577-8031_577-8030insTT		intron_variant		3

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

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.932

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.969

Gnomad4 OTH AF: 0.896

Alfa AF: 0.916 Hom.: 7867

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Combined oxidative phosphorylation deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34687863; hg19: chr6-44266648;