19-38922088-GT-GTT

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017827.4(SARS2):​c.393+149dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,188 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SARS2 NM_017827.4 intron
• Clinical Significance: Not reported in ClinVar
• 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: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia, Orphanet
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ENSG00000269547 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017827.4. 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+149dupA		intron	N/A	NP_060297.1	Q9NP81-1
	SARS2	NM_001145901.2		c.394-11dupA		intron	N/A	NP_001139373.1	Q9NP81-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SARS2	ENST00000221431.11	TSL:1 MANE Select	c.393+149dupA		intron	N/A	ENSP00000221431.6	Q9NP81-1
	ENSG00000269547	ENST00000599996.1	TSL:2	c.600+149dupA		intron	N/A	ENSP00000472465.1	M0R2C6
	SARS2	ENST00000598831.6	TSL:5	c.393+149dupA		intron	N/A	ENSP00000468865.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000442 AC: 1 AN: 226062 AF XY: 0.00000815

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000100

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447188 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 719088

African (AFR) AF: 0.00 AC: 0 AN: 33034

American (AMR) AF: 0.00 AC: 0 AN: 42018

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25870

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 84504

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104366

Other (OTH) AF: 0.00 AC: 0 AN: 59928

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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;