19-38915475-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBS1_Supporting

The NM_017827.4(SARS2):c.*131C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000532 in 1,090,314 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

SARS2
NM_017827.4 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.439

Publications

0 publications found

Variant links:

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

SARS2 links:

ENSG00000269547 (HGNC:):

ENSG00000269547 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13818973).

BS1

Variant frequency is greater than expected in population sas. GnomAdExome4 allele frequency = 0.0000597 (56/938174) while in subpopulation SAS AF = 0.000576 (38/65920). AF 95% confidence interval is 0.000431. There are 0 homozygotes in GnomAdExome4. There are 41 alleles in the male GnomAdExome4 subpopulation. Median coverage is 12. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*131C>T		3_prime_UTR	Exon 16 of 16	NP_060297.1	Q9NP81-1
	SARS2	NM_001145901.2		c.*131C>T		3_prime_UTR	Exon 17 of 17	NP_001139373.1	Q9NP81-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SARS2	ENST00000221431.11	TSL:1 MANE Select	c.*131C>T		3_prime_UTR	Exon 16 of 16	ENSP00000221431.6	Q9NP81-1
ENSG00000269547	ENST00000599996.1	TSL:2	c.*131C>T		3_prime_UTR	Exon 20 of 20	ENSP00000472465.1	M0R2C6
SARS2	ENST00000598831.6	TSL:5	c.1564C>T	p.Pro522Ser	missense	Exon 17 of 17	ENSP00000468865.2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000598

AC:

AN:

167158

AF XY:

0.0000770

show subpopulations

Gnomad AFR exome

AF:

0.0000807

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:

0.0000374

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000597

AC:

AN:

938174

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

476564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22770

American (AMR)

AF:

0.00

AC:

AN:

33712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18466

East Asian (EAS)

AF:

0.00

AC:

AN:

36818

South Asian (SAS)

AF:

0.000576

AC:

AN:

65920

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2904

European-Non Finnish (NFE)

AF:

0.0000250

AC:

AN:

679804

Other (OTH)

AF:

0.0000236

AC:

AN:

42390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41430

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000334

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.21

CADD

Benign

4.2

(source)

DANN

Benign

0.66

FATHMM_MKL

Benign

0.090

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

PhyloP100

0.44

Vest4

0.15

MVP

0.90

GERP RS

-0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over