chr19-38915622-T-C

Variant names:

• chr19-38915622-T-C
• rs1481233791
• NM_017827.4:c.1541A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017827.4(SARS2):​c.1541A>G​(p.Gln514Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 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)
• Consequence: SARS2 NM_017827.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.439

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]

ENSG00000269547 (HGNC:):

ACMG classification

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=0.12330976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARS2	NM_017827.4	c.1541A>G	p.Gln514Arg	missense_variant	Exon 16 of 16	ENST00000221431.11	NP_060297.1
SARS2	NM_001145901.2	c.1547A>G	p.Gln516Arg	missense_variant	Exon 17 of 17		NP_001139373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11	c.1541A>G	p.Gln514Arg	missense_variant	Exon 16 of 16	1	NM_017827.4	ENSP00000221431.6
ENSG00000269547	ENST00000599996.1	c.1748A>G	p.Gln583Arg	missense_variant	Exon 20 of 20	2		ENSP00000472465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	7.5
DANN	Benign	0.90
DEOGEN2	Benign	0.050	T;.;T;.;.
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.051	N
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.69	N;.;.;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.71	N;.;.;.;.
REVEL	Benign	0.042
Sift	Pathogenic	0.0	D;.;.;.;.
Sift4G	Uncertain	0.058	T;D;T;D;D
Polyphen		0.0	B;.;.;.;.
Vest4		0.12
MutPred		0.19		Gain of methylation at Q514 (P = 0.0169);.;Gain of methylation at Q514 (P = 0.0169);.;.;
MVP		0.70
MPC		0.33
ClinPred		0.12	T
GERP RS		-2.0
Varity_R		0.19
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1481233791; hg19: chr19-39406262;