Variant chr20-45363631-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_033542.4(SYS1):c.100C>T(p.Leu34Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00598 in 1,584,242 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 13 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 56 hom. )

Consequence

SYS1
NM_033542.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

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:

SYS1 (HGNC:):

SYS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 20-45363631-C-T is Benign according to our data. Variant chr20-45363631-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652348.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.16 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYS1	NM_033542.4 linkuse as main transcript	c.100C>T	p.Leu34Leu	synonymous_variant	2/4	ENST00000243918.10	NP_291020.1	Q8N2H4-1
SYS1	NM_001197129.2 linkuse as main transcript	c.100C>T	p.Leu34Leu	synonymous_variant	3/5		NP_001184058.1	Q8N2H4-1
SYS1	NM_001099791.3 linkuse as main transcript	c.100C>T	p.Leu34Leu	synonymous_variant	2/4		NP_001093261.1	Q8N2H4-2
SYS1-DBNDD2	NR_003189.2 linkuse as main transcript	n.250C>T		non_coding_transcript_exon_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYS1	ENST00000243918.10 linkuse as main transcript	c.100C>T	p.Leu34Leu	synonymous_variant	2/4	1	NM_033542.4	ENSP00000243918.5		Q8N2H4-1
SYS1-DBNDD2	ENST00000458187.5 linkuse as main transcript	n.100C>T		non_coding_transcript_exon_variant	1/6	5		ENSP00000457768.1		H3BUS1

Frequencies

GnomAD3 genomes

AF:

0.00555

AC:

845

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.0385

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00539

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00598

AC:

1169

AN:

195454

Hom.:

AF XY:

0.00585

AC XY:

620

AN XY:

105976

show subpopulations

Gnomad AFR exome

AF:

0.00120

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00151

Gnomad FIN exome

AF:

0.0346

Gnomad NFE exome

AF:

0.00593

Gnomad OTH exome

AF:

0.00529

GnomAD4 exome

AF:

0.00603

AC:

8632

AN:

1431924

Hom.:

Cov.:

AF XY:

0.00583

AC XY:

4139

AN XY:

710114

show subpopulations

Gnomad4 AFR exome

AF:

0.000762

Gnomad4 AMR exome

AF:

0.00149

Gnomad4 ASJ exome

AF:

0.0000781

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00146

Gnomad4 FIN exome

AF:

0.0329

Gnomad4 NFE exome

AF:

0.00592

Gnomad4 OTH exome

AF:

0.00482

GnomAD4 genome

AF:

0.00554

AC:

844

AN:

152318

Hom.:

Cov.:

AF XY:

0.00701

AC XY:

522

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0385

Gnomad4 NFE

AF:

0.00539

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00465

Hom.:

Bravo

AF:

0.00278

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

SYS1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.88

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