rs2245717

Variant names:

• chr20-45367240-T-A
• rs2245717
• ENST00000457307.1:n.*494T>A

Your query was ambiguous. Multiple possible variants found:

• chr20-45367240-T-A
• chr20-45367240-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000457307.1(SYS1):​n.*494T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SYS1 ENST00000457307.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 25 publications found

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-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]

ACMG classification

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 (BayesDel_noAF=-0.5).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457307.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYS1	NM_033542.4	MANE Select	c.*125T>A		3_prime_UTR	Exon 4 of 4	NP_291020.1
	SYS1	NM_001197129.2		c.*125T>A		3_prime_UTR	Exon 5 of 5	NP_001184058.1
	SYS1	NM_001099791.3		c.230+1554T>A		intron	N/A	NP_001093261.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYS1	ENST00000457307.1	TSL:1	n.*494T>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000397601.1
	SYS1	ENST00000243918.10	TSL:1 MANE Select	c.*125T>A		3_prime_UTR	Exon 4 of 4	ENSP00000243918.5
	SYS1	ENST00000457307.1	TSL:1	n.*494T>A		3_prime_UTR	Exon 4 of 4	ENSP00000397601.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1354444 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 662670

African (AFR) AF: 0.00 AC: 0 AN: 30490

American (AMR) AF: 0.00 AC: 0 AN: 29000

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20066

East Asian (EAS) AF: 0.00 AC: 0 AN: 38468

South Asian (SAS) AF: 0.00 AC: 0 AN: 69428

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1061816

Other (OTH) AF: 0.00 AC: 0 AN: 56014

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2245717; hg19: chr20-43995880;