chr20-45367240-T-G

Position:

• chr20-45367240-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033542.4(SYS1):​c.*125T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.772 in 1,506,226 control chromosomes in the GnomAD database, including 450,965 homozygotes. 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: 𝑓 0.79 (47604 hom., cov: 31)
  • Exomes 𝑓: 0.77 (403361 hom.)
• Consequence: SYS1 NM_033542.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

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]

SYS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYS1	NM_033542.4	c.*125T>G		3_prime_UTR_variant	4/4	ENST00000243918.10	NP_291020.1
SYS1	NM_001197129.2	c.*125T>G		3_prime_UTR_variant	5/5		NP_001184058.1
SYS1	NM_001099791.3	c.230+1554T>G		intron_variant			NP_001093261.1
SYS1-DBNDD2	NR_003189.2	n.380+1554T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYS1	ENST00000243918.10	c.*125T>G		3_prime_UTR_variant	4/4	1	NM_033542.4	ENSP00000243918.5
SYS1-DBNDD2	ENST00000458187.5	n.230+1554T>G		intron_variant		5		ENSP00000457768.1

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119884 AN: 151958 Hom.: 47547 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.770 AC: 1043248 AN: 1354150 Hom.: 403361 Cov.: 47 AF XY: 0.772 AC XY: 511200 AN XY: 662502

Gnomad4 AFR exome AF: 0.856

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.832

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.747

Gnomad4 NFE exome AF: 0.773

Gnomad4 OTH exome AF: 0.769

GnomAD4 genome AF: 0.789 AC: 119999 AN: 152076 Hom.: 47604 Cov.: 31 AF XY: 0.787 AC XY: 58529 AN XY: 74334

Gnomad4 AFR AF: 0.852

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.788

Alfa AF: 0.781 Hom.: 48740

Bravo AF: 0.788

Asia WGS AF: 0.724 AC: 2518 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2245717; hg19: chr20-43995880; COSMIC: COSV54782100; COSMIC: COSV54782100;