chr1-109214096-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_006513.4(SARS1):c.104A>G(p.Gln35Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

SARS1
NM_006513.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.57

Publications

0 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048615217).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00019 (29/152356) while in subpopulation AFR AF = 0.000697 (29/41590). AF 95% confidence interval is 0.000498. There are 1 homozygotes in GnomAd4. There are 15 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_006513.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SARS1	NM_006513.4	MANE Select	c.104A>G	p.Gln35Arg	missense	Exon 1 of 11	NP_006504.2
SARS1	NM_001330669.1		c.104A>G	p.Gln35Arg	missense	Exon 1 of 12	NP_001317598.1	Q5T5C7
SARS1	NR_034072.1		n.204A>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SARS1	ENST00000234677.7	TSL:1 MANE Select	c.104A>G	p.Gln35Arg	missense	Exon 1 of 11	ENSP00000234677.2	P49591
SARS1	ENST00000943750.1		c.104A>G	p.Gln35Arg	missense	Exon 1 of 13	ENSP00000613809.1
SARS1	ENST00000943751.1		c.104A>G	p.Gln35Arg	missense	Exon 1 of 12	ENSP00000613810.1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000478

AC:

AN:

251062

AF XY:

0.0000442

show subpopulations

Gnomad AFR exome

AF:

0.000739

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000889

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33466

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111972

Other (OTH)

AF:

0.0000166

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.440

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:

0.000190

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000697

AC:

AN:

41590

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.000154

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.055

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.77

M_CAP

Benign

0.0052

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

2.6

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.090

REVEL

Benign

0.059

Sift

Benign

0.047

Sift4G

Benign

0.066

Polyphen

0.0

Vest4

0.16

MVP

0.45

MPC

0.78

ClinPred

0.19

GERP RS

4.4

PromoterAI

0.037

Neutral

(source)

Varity_R

0.34

gMVP

0.26

Mutation Taster

=74/26

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

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