19-38915527-C-G

Position:

• chr19-38915527-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017827.4(SARS2):​c.*79G>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 0.381 in 1,552,294 control chromosomes in the GnomAD database, including 120,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17371 hom., cov: 31)
  • Exomes 𝑓: 0.37 (103317 hom.)
• Consequence: SARS2 NM_017827.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.883

Genes affected

SARS2 (HGNC:17697): (seryl-tRNA synthetase 2, mitochondrial) This gene encodes the mitochondrial seryl-tRNA synthethase precursor, a member of the class II tRNA synthetase family. The mature enzyme catalyzes the ligation of Serine to tRNA(Ser) and participates in the biosynthesis of selenocysteinyl-tRNA(sec) in mitochondria. The enzyme contains an N-terminal tRNA binding domain and a core catalytic domain. It functions in a homodimeric form, which is stabilized by tRNA binding. This gene is regulated by a bidirectional promoter that also controls the expression of mitochondrial ribosomal protein S12. Both genes are within the critical interval for the autosomal dominant deafness locus DFNA4 and might be linked to this disease. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-38915527-C-G is Benign according to our data. Variant chr19-38915527-C-G is described in ClinVar as [Benign]. Clinvar id is 329207.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARS2	NM_017827.4	c.*79G>C		3_prime_UTR_variant	16/16	ENST00000221431.11	NP_060297.1
SARS2	NM_001145901.2	c.*79G>C		3_prime_UTR_variant	17/17		NP_001139373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11	c.*79G>C		3_prime_UTR_variant	16/16	1	NM_017827.4	ENSP00000221431	P4

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69810 AN: 151754 Hom.: 17335 Cov.: 31

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.446

GnomAD3 exomes AF: 0.439 AC: 100015 AN: 227662 Hom.: 24005 AF XY: 0.426 AC XY: 52990 AN XY: 124358

Gnomad AFR exome AF: 0.613

Gnomad AMR exome AF: 0.550

Gnomad ASJ exome AF: 0.441

Gnomad EAS exome AF: 0.752

Gnomad SAS exome AF: 0.380

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.373 AC: 522100 AN: 1400422 Hom.: 103317 Cov.: 25 AF XY: 0.372 AC XY: 259507 AN XY: 697554

Gnomad4 AFR exome AF: 0.619

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.755

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.460

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.460 AC: 69898 AN: 151872 Hom.: 17371 Cov.: 31 AF XY: 0.472 AC XY: 35035 AN XY: 74234

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.447

Alfa AF: 0.402 Hom.: 2415

Bravo AF: 0.473

Asia WGS AF: 0.556 AC: 1932 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.7
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs9403; hg19: chr19-39406167;