rs140717526

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006513.4(SARS1):c.1160G>A(p.Gly387Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0117 in 1,604,458 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0089 ( 15 hom., cov: 32)

Exomes 𝑓: 0.012 ( 143 hom. )

Consequence

SARS1
NM_006513.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.58

Publications

12 publications found

Variant links:

Genes affected

SARS1 (HGNC:10537): (seryl-tRNA synthetase 1) This gene belongs to the class II amino-acyl tRNA family. The encoded enzyme catalyzes the transfer of L-serine to tRNA (Ser) and is related to bacterial and yeast counterparts. Multiple alternatively spliced transcript variants have been described but the biological validity of all variants is unknown. [provided by RefSeq, Jul 2010]

SARS1 Gene-Disease associations (from GenCC):

hereditary peripheral neuropathy
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
neurodevelopmental disorder
Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, G2P
neurodevelopmental disorder with microcephaly, ataxia, and seizures
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, G2P
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009588867).

BP6

Variant 1-109236451-G-A is Benign according to our data. Variant chr1-109236451-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 774395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00892 (1358/152214) while in subpopulation NFE AF = 0.0142 (963/68018). AF 95% confidence interval is 0.0134. There are 15 homozygotes in GnomAd4. There are 636 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 15 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006513.4. 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
	SARS1	NM_006513.4	MANE Select	c.1160G>A	p.Gly387Glu	missense	Exon 9 of 11	NP_006504.2
	SARS1	NM_001330669.1		c.1160G>A	p.Gly387Glu	missense	Exon 9 of 12	NP_001317598.1	Q5T5C7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SARS1	ENST00000234677.7	TSL:1 MANE Select	c.1160G>A	p.Gly387Glu	missense	Exon 9 of 11	ENSP00000234677.2	P49591
SARS1	ENST00000943750.1		c.1277G>A	p.Gly426Glu	missense	Exon 10 of 13	ENSP00000613809.1
SARS1	ENST00000943751.1		c.1277G>A	p.Gly426Glu	missense	Exon 10 of 12	ENSP00000613810.1

Frequencies

GnomAD3 genomes

AF:

0.00893

AC:

1358

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00307

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.00885

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00892

AC:

2243

AN:

251456

AF XY:

0.00868

show subpopulations

Gnomad AFR exome

AF:

0.00308

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.0230

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00189

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0120

AC:

17368

AN:

1452244

Hom.:

143

Cov.:

AF XY:

0.0116

AC XY:

8377

AN XY:

720070

show subpopulations

African (AFR)

AF:

0.00276

AC:

AN:

33344

American (AMR)

AF:

0.00541

AC:

241

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.0237

AC:

618

AN:

26068

East Asian (EAS)

AF:

0.0000762

AC:

AN:

39372

South Asian (SAS)

AF:

0.00343

AC:

295

AN:

86114

European-Finnish (FIN)

AF:

0.00305

AC:

163

AN:

53358

Middle Eastern (MID)

AF:

0.0108

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.0138

AC:

15211

AN:

1103834

Other (OTH)

AF:

0.0114

AC:

683

AN:

59840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

916

1833

2749

3666

4582

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

578

1156

1734

2312

2890

<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:

0.00892

AC:

1358

AN:

152214

Hom.:

Cov.:

AF XY:

0.00855

AC XY:

636

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00306

AC:

127

AN:

41528

American (AMR)

AF:

0.00884

AC:

135

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00249

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0142

AC:

963

AN:

68018

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

129

193

258

322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0127

Hom.:

Bravo

AF:

0.00940

TwinsUK

AF:

0.0154

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0177

AC:

152

ExAC

AF:

0.00937

AC:

1137

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0147

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.75

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

MetaRNN

Benign

0.0096

MetaSVM

Benign

-0.71

MutationAssessor

Benign

1.4

PhyloP100

3.6

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.32

Sift

Benign

0.069

Sift4G

Benign

0.16

Polyphen

0.18

Vest4

0.53

MVP

0.50

MPC

1.8

ClinPred

0.030

GERP RS

6.1

Varity_R

0.46

gMVP

0.80

Mutation Taster

=82/18

polymorphism

(source)

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

Publications

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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