rs200395107

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033542.4(SYS1):c.8G>C(p.Gly3Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000109 in 1,560,556 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SYS1
NM_033542.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.26

Publications

1 publications found

Variant links:

Genes affected

SYS1 (HGNC:16162): (SYS1 golgi trafficking protein) SYS1 forms a complex with ADP-ribosylation factor-related protein ARFRP1 (MIM 604699) and targets ARFRP1 to the Golgi apparatus (Behnia et al., 2004 [PubMed 15077113]).[supplied by OMIM, Aug 2009]

SYS1 links:

SYS1-DBNDD2 (HGNC:33535): (SYS1-DBNDD2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription from the neighboring SYS1 Golgi-localized integral membrane protein homolog and dysbindin domain containing 2 (DBNDD2) genes. The read-through transcript includes the majority of exons from each individual gene, but it would be subject to nonsense-mediated mRNA decay (NMD) and is therefore predicted to be non-coding. [provided by RefSeq, Oct 2010]

SYS1-DBNDD2 links:

ENSG00000305954 (HGNC:):

ENSG00000305954 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011702985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033542.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYS1	NM_033542.4	MANE Select	c.8G>C	p.Gly3Ala	missense	Exon 2 of 4	NP_291020.1	Q8N2H4-1
SYS1	NM_001197129.2		c.8G>C	p.Gly3Ala	missense	Exon 3 of 5	NP_001184058.1	Q8N2H4-1
SYS1	NM_001099791.3		c.8G>C	p.Gly3Ala	missense	Exon 2 of 4	NP_001093261.1	Q8N2H4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYS1	ENST00000243918.10	TSL:1 MANE Select	c.8G>C	p.Gly3Ala	missense	Exon 2 of 4	ENSP00000243918.5	Q8N2H4-1
SYS1	ENST00000453003.1	TSL:1	c.8G>C	p.Gly3Ala	missense	Exon 1 of 3	ENSP00000406879.1	Q5QPU8
SYS1	ENST00000457307.1	TSL:1	n.8G>C		non_coding_transcript_exon	Exon 2 of 4	ENSP00000397601.1	F8WB21

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152278

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000284

AC:

AN:

168994

AF XY:

0.000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00500

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000875

Gnomad OTH exome

AF:

0.000218

GnomAD4 exome

AF:

0.000106

AC:

149

AN:

1408278

Hom.:

Cov.:

AF XY:

0.000119

AC XY:

AN XY:

696912

show subpopulations

African (AFR)

AF:

0.0000309

AC:

AN:

32378

American (AMR)

AF:

0.00

AC:

AN:

38130

Ashkenazi Jewish (ASJ)

AF:

0.00499

AC:

124

AN:

24828

East Asian (EAS)

AF:

0.00

AC:

AN:

36948

South Asian (SAS)

AF:

0.00

AC:

AN:

80954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45082

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5660

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

1085926

Other (OTH)

AF:

0.000223

AC:

AN:

58372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.000138

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41478

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5208

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68046

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000459

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000103

AC:

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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

Eigen

Benign

-0.010

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.019

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.78

PhyloP100

4.3

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.055

Sift

Benign

0.18

Sift4G

Benign

0.34

Polyphen

0.0010

Vest4

0.088

MVP

0.076

MPC

0.38

ClinPred

0.21

GERP RS

5.7

PromoterAI

0.18

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.48

gMVP

0.33

Mutation Taster

=53/47

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