6-87514298-C-T

Position:

• chr6-87514298-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020320.5(RARS2):​c.*115G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0979 in 639,874 control chromosomes in the GnomAD database, including 3,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1151 hom., cov: 28)
  • Exomes 𝑓: 0.090 (2339 hom.)
• Consequence: RARS2 NM_020320.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0640

Genes affected

RARS2 (HGNC:21406): (arginyl-tRNA synthetase 2, mitochondrial) This nuclear gene encodes a protein that localizes to the mitochondria, where it catalyzes the transfer of L-arginine to its cognate tRNA, an important step in translation of mitochondrially-encoded proteins. Defects in this gene are a cause of pontocerebellar hypoplasia type 6 (PCH6). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 6-87514298-C-T is Benign according to our data. Variant chr6-87514298-C-T is described in ClinVar as [Benign]. Clinvar id is 1294199.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RARS2	NM_020320.5	c.*115G>A		3_prime_UTR_variant	20/20	ENST00000369536.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RARS2	ENST00000369536.10	c.*115G>A		3_prime_UTR_variant	20/20	1	NM_020320.5	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 17862 AN: 140860 Hom.: 1143 Cov.: 28

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.0897 AC: 44730 AN: 498926 Hom.: 2339 AF XY: 0.0898 AC XY: 24160 AN XY: 269062

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.113

Gnomad4 ASJ exome AF: 0.0776

Gnomad4 EAS exome AF: 0.138

Gnomad4 SAS exome AF: 0.0956

Gnomad4 FIN exome AF: 0.0858

Gnomad4 NFE exome AF: 0.0822

Gnomad4 OTH exome AF: 0.0934

GnomAD4 genome AF: 0.127 AC: 17905 AN: 140948 Hom.: 1151 Cov.: 28 AF XY: 0.129 AC XY: 8713 AN XY: 67740

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.0913

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0362 Hom.: 29

Bravo AF: 0.128

Asia WGS AF: 0.152 AC: 528 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.19

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4615353; hg19: chr6-88224016;