chr19-38915708-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1
The NM_017827.4(SARS2):c.1455C>T(p.Leu485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,613,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
SARS2
NM_017827.4 synonymous
NM_017827.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.96
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 19-38915708-G-A is Benign according to our data. Variant chr19-38915708-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1604822.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.96 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000138 (21/152154) while in subpopulation AFR AF= 0.000362 (15/41448). AF 95% confidence interval is 0.000222. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SARS2 | NM_017827.4 | c.1455C>T | p.Leu485= | synonymous_variant | 16/16 | ENST00000221431.11 | |
SARS2 | NM_001145901.2 | c.1461C>T | p.Leu487= | synonymous_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SARS2 | ENST00000221431.11 | c.1455C>T | p.Leu485= | synonymous_variant | 16/16 | 1 | NM_017827.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250186Hom.: 0 AF XY: 0.0000518 AC XY: 7AN XY: 135198
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GnomAD4 exome AF: 0.0000356 AC: 52AN: 1460924Hom.: 0 Cov.: 33 AF XY: 0.0000413 AC XY: 30AN XY: 726600
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 04, 2021 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at