Variant 20-45363539-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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:):

SYS1-DBNDD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SYS1	NM_033542.4 linkuse as main transcript	c.8G>C	p.Gly3Ala	missense_variant	2/4	ENST00000243918.10
SYS1-DBNDD2	NR_003189.2 linkuse as main transcript	n.158G>C		non_coding_transcript_exon_variant	2/6
SYS1	NM_001197129.2 linkuse as main transcript	c.8G>C	p.Gly3Ala	missense_variant	3/5
SYS1	NM_001099791.3 linkuse as main transcript	c.8G>C	p.Gly3Ala	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYS1	ENST00000243918.10 linkuse as main transcript	c.8G>C	p.Gly3Ala	missense_variant	2/4	1	NM_033542.4	P1	Q8N2H4-1

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

GnomAD3 exomes

AF:

0.000284

AC:

AN:

168994

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

91394

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 SAS 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

Gnomad4 AFR exome

AF:

0.0000309

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00499

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.000223

GnomAD4 genome

AF:

0.000138

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000459

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.000103

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2022

The c.8G>C (p.G3A) alteration is located in exon 3 (coding exon 1) of the SYS1 gene. This alteration results from a G to C substitution at nucleotide position 8, causing the glycine (G) at amino acid position 3 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.39

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;.;.

Eigen

Benign

-0.010

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.74

M_CAP

Benign

0.019

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.78

N;N;N;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.4

D;D;D;D

REVEL

Benign

0.055

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.0010

B;B;.;.

Vest4

0.088

MVP

0.076

MPC

0.38

ClinPred

0.21

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.48

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over