19-38915373-AGCCCAGAC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_017827.4(SARS2):c.*225_*232del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00133 in 584,894 control chromosomes in the GnomAD database, including 17 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (16 hom.)
• Consequence: SARS2 NM_017827.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.34

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 -10 ACMG points.

• BP6: Variant 19-38915373-AGCCCAGAC-A is Benign according to our data. Variant chr19-38915373-AGCCCAGAC-A is described in ClinVar as [Likely_benign]. Clinvar id is 1188786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000604 (92/152240) while in subpopulation SAS AF= 0.018 (87/4830). AF 95% confidence interval is 0.015. There are 1 homozygotes in gnomad4. There are 70 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SARS2	NM_017827.4	c.*225_*232del		3_prime_UTR_variant	16/16	ENST00000221431.11
SARS2	NM_001145901.2	c.*225_*232del		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SARS2	ENST00000221431.11	c.*225_*232del		3_prime_UTR_variant	16/16	1	NM_017827.4	P4

Frequencies

GnomAD3 genomes AF: 0.000592 AC: 90 AN: 152122 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0176

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00200 AC: 116 AN: 57940 Hom.: 5 AF XY: 0.00250 AC XY: 73 AN XY: 29148

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0188

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00104

GnomAD4 exome AF: 0.00159 AC: 686 AN: 432654 Hom.: 16 AF XY: 0.00233 AC XY: 526 AN XY: 225840

Gnomad4 AFR exome AF: 0.0000818

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0160

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000385

Gnomad4 OTH exome AF: 0.000433

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152240 Hom.: 1 Cov.: 32 AF XY: 0.000941 AC XY: 70 AN XY: 74424

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000256 Hom.: 0

Bravo AF: 0.000147

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs542688500; hg19: chr19-39406013;