chr11-78436471-G-A

Position:

• chr11-78436471-G-A

Variant summary

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

The NM_024678.6(NARS2):​c.*199C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0165 in 580,212 control chromosomes in the GnomAD database, including 709 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (530 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (179 hom.)
• Consequence: NARS2 NM_024678.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.518

Genes affected

NARS2 (HGNC:26274): (asparaginyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of asparagine to tRNA molecules. Mutations in this gene have been associated with combined oxidative phosphorylation deficiency 24 (COXPD24). [provided by RefSeq, Mar 2015]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-78436471-G-A is Benign according to our data. Variant chr11-78436471-G-A is described in ClinVar as [Benign]. Clinvar id is 1246376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NARS2	NM_024678.6	c.*199C>T		3_prime_UTR_variant	14/14	ENST00000281038.10
NARS2	NM_001243251.2	c.*199C>T		3_prime_UTR_variant	14/14
NARS2	XM_011545253.3	c.*199C>T		3_prime_UTR_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NARS2	ENST00000281038.10	c.*199C>T		3_prime_UTR_variant	14/14	1	NM_024678.6	P1
	ENST00000534168.1	n.36-7177G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7056 AN: 151962 Hom.: 529 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0398

GnomAD4 exome AF: 0.00585 AC: 2505 AN: 428132 Hom.: 179 Cov.: 6 AF XY: 0.00469 AC XY: 1058 AN XY: 225568

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000310

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000230

Gnomad4 OTH exome AF: 0.0111

GnomAD4 genome AF: 0.0466 AC: 7081 AN: 152080 Hom.: 530 Cov.: 32 AF XY: 0.0457 AC XY: 3397 AN XY: 74336

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.0158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.0394

Alfa AF: 0.0301 Hom.: 77

Bravo AF: 0.0540

Asia WGS AF: 0.0110 AC: 40 AN: 3478

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 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs73504911; hg19: chr11-78147517;