20-45363631-C-T

Variant names:

• chr20-45363631-C-T
• rs41307197
• NM_033542.4:c.100C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16
• Publications: 2 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]

ENSG00000305954 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYS1	NM_033542.4	MANE Select	c.100C>T	p.Leu34Leu	synonymous	Exon 2 of 4	NP_291020.1	Q8N2H4-1
	SYS1	NM_001197129.2		c.100C>T	p.Leu34Leu	synonymous	Exon 3 of 5	NP_001184058.1	Q8N2H4-1
	SYS1	NM_001099791.3		c.100C>T	p.Leu34Leu	synonymous	Exon 2 of 4	NP_001093261.1	Q8N2H4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYS1	ENST00000243918.10	TSL:1 MANE Select	c.100C>T	p.Leu34Leu	synonymous	Exon 2 of 4	ENSP00000243918.5	Q8N2H4-1
	SYS1	ENST00000453003.1	TSL:1	c.100C>T	p.Leu34Leu	synonymous	Exon 1 of 3	ENSP00000406879.1	Q5QPU8
	SYS1	ENST00000457307.1	TSL:1	n.100C>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000397601.1	F8WB21

Frequencies

GnomAD3 genomes AF: 0.00555 AC: 845 AN: 152200 Hom.: 13 Cov.: 33

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

GnomAD2 exomes AF: 0.00598 AC: 1169 AN: 195454 AF XY: 0.00585

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 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.: 56 Cov.: 31 AF XY: 0.00583 AC XY: 4139 AN XY: 710114

African (AFR) AF: 0.000762 AC: 25 AN: 32824

American (AMR) AF: 0.00149 AC: 60 AN: 40140

Ashkenazi Jewish (ASJ) AF: 0.0000781 AC: 2 AN: 25612

East Asian (EAS) AF: 0.00 AC: 0 AN: 37862

South Asian (SAS) AF: 0.00146 AC: 120 AN: 82460

European-Finnish (FIN) AF: 0.0329 AC: 1627 AN: 49478

Middle Eastern (MID) AF: 0.00140 AC: 8 AN: 5732

European-Non Finnish (NFE) AF: 0.00592 AC: 6504 AN: 1098500

Other (OTH) AF: 0.00482 AC: 286 AN: 59316

GnomAD4 genome AF: 0.00554 AC: 844 AN: 152318 Hom.: 13 Cov.: 33 AF XY: 0.00701 AC XY: 522 AN XY: 74468

African (AFR) AF: 0.000986 AC: 41 AN: 41578

American (AMR) AF: 0.000784 AC: 12 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.0385 AC: 409 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00539 AC: 367 AN: 68026

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00465 Hom.: 2

Bravo AF: 0.00278

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.88
PhyloP100		1.2
PromoterAI		0.014	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs41307197; hg19: chr20-43992271;