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. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_001145901.2(SARS2):​c.394-11delA 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_001145901.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.877
• Publications: 0 publications found

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]

SARS2 Gene-Disease associations (from GenCC):

• hyperuricemia-pulmonary hypertension-renal failure-alkalosis syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000269547 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145901.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS2	NM_017827.4	MANE Select	c.393+149delA		intron	N/A	NP_060297.1
	SARS2	NM_001145901.2		c.394-11delA		intron	N/A	NP_001139373.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS2	ENST00000221431.11	TSL:1 MANE Select	c.393+149delA		intron	N/A	ENSP00000221431.6
	ENSG00000269547	ENST00000599996.1	TSL:2	c.600+149delA		intron	N/A	ENSP00000472465.1
	SARS2	ENST00000598831.6	TSL:5	c.393+149delA		intron	N/A	ENSP00000468865.2

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

GnomAD2 exomes AF: 0.000801 AC: 181 AN: 226062 AF XY: 0.000611

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 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

African (AFR) AF: 0.00929 AC: 307 AN: 33034

American (AMR) AF: 0.000809 AC: 34 AN: 42018

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25870

East Asian (EAS) AF: 0.00 AC: 0 AN: 38852

South Asian (SAS) AF: 0.0000355 AC: 3 AN: 84504

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52864

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5752

European-Non Finnish (NFE) AF: 0.000109 AC: 120 AN: 1104364

Other (OTH) AF: 0.000751 AC: 45 AN: 59928

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

African (AFR) AF: 0.0102 AC: 422 AN: 41498

American (AMR) AF: 0.000919 AC: 14 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68008

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00148 Hom.: 0

Bravo AF: 0.00317

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.88

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

Other links and lift over

dbSNP: rs375344827; hg19: chr19-39412728;