NM_020320.5:c.*101delT

Variant names:

• chr6-87514311-CA-C
• rs5878032
• NM_020320.5:c.*101delT

Variant summary

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

The NM_020320.5(RARS2):​c.*101delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 562,758 control chromosomes in the GnomAD database, including 6,015 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (5428 hom., cov: 0)
  • Exomes 𝑓: 0.32 (587 hom.)
• Consequence: RARS2 NM_020320.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.613
• Publications: 1 publications found

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]

RARS2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• pontocerebellar hypoplasia type 6

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Laboratory for Molecular Medicine, Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-87514311-CA-C is Benign according to our data. Variant chr6-87514311-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1291574.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020320.5. 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
	RARS2	NM_020320.5	MANE Select	c.*101delT		3_prime_UTR	Exon 20 of 20	NP_064716.2	Q5T160
	RARS2	NM_001318785.2		c.*101delT		3_prime_UTR	Exon 19 of 19	NP_001305714.1	H0UI22
	RARS2	NM_001350507.2		c.*101delT		3_prime_UTR	Exon 21 of 21	NP_001337436.1	H0UI22

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RARS2	ENST00000369536.10	TSL:1 MANE Select	c.*101delT		3_prime_UTR	Exon 20 of 20	ENSP00000358549.5	Q5T160
	RARS2	ENST00000685408.1		c.*101delT		3_prime_UTR	Exon 21 of 21	ENSP00000509026.1	H0UI22
	RARS2	ENST00000689174.1		c.*101delT		3_prime_UTR	Exon 20 of 20	ENSP00000510542.1	H0UI22

Frequencies

GnomAD3 genomes AF: 0.358 AC: 40103 AN: 112054 Hom.: 5427 Cov.: 0

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.360

GnomAD4 exome AF: 0.324 AC: 146095 AN: 450676 Hom.: 587 AF XY: 0.326 AC XY: 78850 AN XY: 242066

African (AFR) AF: 0.297 AC: 3032 AN: 10206

American (AMR) AF: 0.385 AC: 6919 AN: 17994

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 4214 AN: 12518

East Asian (EAS) AF: 0.310 AC: 6003 AN: 19366

South Asian (SAS) AF: 0.351 AC: 16838 AN: 47984

European-Finnish (FIN) AF: 0.327 AC: 8983 AN: 27496

Middle Eastern (MID) AF: 0.318 AC: 481 AN: 1514

European-Non Finnish (NFE) AF: 0.317 AC: 92935 AN: 292840

Other (OTH) AF: 0.322 AC: 6690 AN: 20758

GnomAD4 genome AF: 0.358 AC: 40096 AN: 112082 Hom.: 5428 Cov.: 0 AF XY: 0.360 AC XY: 19225 AN XY: 53374

African (AFR) AF: 0.303 AC: 8725 AN: 28766

American (AMR) AF: 0.453 AC: 5223 AN: 11518

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1051 AN: 2764

East Asian (EAS) AF: 0.341 AC: 1350 AN: 3960

South Asian (SAS) AF: 0.397 AC: 1426 AN: 3588

European-Finnish (FIN) AF: 0.363 AC: 2173 AN: 5978

Middle Eastern (MID) AF: 0.428 AC: 95 AN: 222

European-Non Finnish (NFE) AF: 0.363 AC: 19321 AN: 53174

Other (OTH) AF: 0.357 AC: 525 AN: 1472

Alfa AF: 0.152 Hom.: 171

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5878032; hg19: chr6-88224029;