dbSNP rs967611001: SARS2:p.Gly513Arg (chr19-38915626-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017827.4(SARS2):c.1537G>C(p.Gly513Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SARS2
NM_017827.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.118

Variant links:

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]

SARS2 links:

ENSG00000269547 (HGNC:):

ENSG00000269547 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11989498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARS2	NM_017827.4 link	c.1537G>C	p.Gly513Arg	missense_variant	Exon 16 of 16	ENST00000221431.11	NP_060297.1	Q9NP81-1
SARS2	NM_001145901.2 link	c.1543G>C	p.Gly515Arg	missense_variant	Exon 17 of 17		NP_001139373.1	Q9NP81-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11 link	c.1537G>C	p.Gly513Arg	missense_variant	Exon 16 of 16	1	NM_017827.4	ENSP00000221431.6		Q9NP81-1
ENSG00000269547	ENST00000599996.1 link	c.1744G>C	p.Gly582Arg	missense_variant	Exon 20 of 20	2		ENSP00000472465.1		M0R2C6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460512

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

T;.;T;.;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.064

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.69

N;.;.;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.32

N;.;.;.;.

REVEL

Benign

0.060

Sift

Uncertain

0.0060

D;.;.;.;.

Sift4G

Benign

0.082

T;T;T;D;T

Polyphen

0.43

B;.;.;.;.

Vest4

0.38

MutPred

0.35

Gain of loop (P = 0.0013);.;Gain of loop (P = 0.0013);.;.;

MVP

0.73

MPC

0.37

ClinPred

0.19

GERP RS

0.90

Varity_R

0.069

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over