chr19-38915623-G-C

Position:

• chr19-38915623-G-C

Variant summary

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

The NM_017827.4(SARS2):​c.1540C>G​(p.Gln514Glu) 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: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23

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=0.17928162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SARS2	NM_017827.4	c.1540C>G	p.Gln514Glu	missense_variant	16/16	ENST00000221431.11	NP_060297.1
SARS2	NM_001145901.2	c.1546C>G	p.Gln516Glu	missense_variant	17/17		NP_001139373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11	c.1540C>G	p.Gln514Glu	missense_variant	16/16	1	NM_017827.4	ENSP00000221431.6
ENSG00000269547	ENST00000599996.1	c.1747C>G	p.Gln583Glu	missense_variant	20/20	2		ENSP00000472465.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 24, 2024

The c.1540C>G (p.Q514E) alteration is located in exon 16 (coding exon 16) of the SARS2 gene. This alteration results from a C to G substitution at nucleotide position 1540, causing the glutamine (Q) at amino acid position 514 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.94
DEOGEN2	Benign	0.049	T;.;T;.;.
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.20	N
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.18	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	0.69	N;.;.;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.51	N;.;.;.;.
REVEL	Benign	0.092
Sift	Pathogenic	0.0	D;.;.;.;.
Sift4G	Uncertain	0.048	D;D;D;D;D
Polyphen		0.055	B;.;.;.;.
Vest4		0.30
MutPred		0.13		Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);.;.;
MVP		0.77
MPC		0.36
ClinPred		0.25	T
GERP RS		2.8
Varity_R		0.20
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr19-39406263;