rs375344827

Variant names:

• chr19-38922088-GT-G
• rs375344827
• NM_017827.4:c.393+149delA

Your query was ambiguous. Multiple possible variants found:

• chr19-38922088-GT-G
• chr19-38922088-GT-GTT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_017827.4(SARS2):​c.393+149delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000599 in 1,599,288 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00036 (1 hom.)
• Consequence: SARS2 NM_017827.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.877

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 19-38922088-GT-G is Benign according to our data. Variant chr19-38922088-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 377294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00292 (444/152102) while in subpopulation AFR AF= 0.0102 (422/41498). AF 95% confidence interval is 0.00937. There are 1 homozygotes in gnomad4. There are 219 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SARS2	NM_017827.4	c.393+149delA		intron_variant	Intron 3 of 15	ENST00000221431.11	NP_060297.1
SARS2	NM_001145901.2	c.394-11delA		intron_variant	Intron 3 of 16		NP_001139373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SARS2	ENST00000221431.11	c.393+149delA		intron_variant	Intron 3 of 15	1	NM_017827.4	ENSP00000221431.6
ENSG00000269547	ENST00000599996.1	c.600+149delA		intron_variant	Intron 7 of 19	2		ENSP00000472465.1

Frequencies

GnomAD3 genomes AF: 0.00291 AC: 443 AN: 151986 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000920

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000801 AC: 181 AN: 226062 Hom.: 0 AF XY: 0.000611 AC XY: 75 AN XY: 122662

Gnomad AFR exome AF: 0.0105

Gnomad AMR exome AF: 0.000571

Gnomad ASJ exome AF: 0.000208

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000350

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000110

Gnomad OTH exome AF: 0.000353

GnomAD4 exome AF: 0.000355 AC: 514 AN: 1447186 Hom.: 1 Cov.: 32 AF XY: 0.000321 AC XY: 231 AN XY: 719088

Gnomad4 AFR exome AF: 0.00929

Gnomad4 AMR exome AF: 0.000809

Gnomad4 ASJ exome AF: 0.0000387

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000355

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000109

Gnomad4 OTH exome AF: 0.000751

GnomAD4 genome AF: 0.00292 AC: 444 AN: 152102 Hom.: 1 Cov.: 33 AF XY: 0.00295 AC XY: 219 AN XY: 74342

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.000919

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00317

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 08, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Feb 08, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs375344827; hg19: chr19-39412728;