4-89836158-A-T

Variant names:

• chr4-89836158-A-T
• rs1372519
• ENST00000618500.4:c.-57T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001375288.1(SNCA):​c.-57T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNCA NM_001375288.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.877
• Publications: 14 publications found

Genes affected

SNCA (HGNC:11138): (synuclein alpha) Alpha-synuclein is a member of the synuclein family, which also includes beta- and gamma-synuclein. Synucleins are abundantly expressed in the brain and alpha- and beta-synuclein inhibit phospholipase D2 selectively. SNCA may serve to integrate presynaptic signaling and membrane trafficking. Defects in SNCA have been implicated in the pathogenesis of Parkinson disease. SNCA peptides are a major component of amyloid plaques in the brains of patients with Alzheimer's disease. Alternatively spliced transcripts encoding different isoforms have been identified for this gene. [provided by RefSeq, Feb 2016]

SNCA-AS1 (HGNC:50600): (SNCA antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375288.1. 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
	SNCA	NM_000345.4	MANE Select	c.-25-466T>A		intron	N/A	NP_000336.1	P37840-1
	SNCA	NM_001375288.1		c.-57T>A		5_prime_UTR	Exon 1 of 6	NP_001362217.1	P37840-1
	SNCA	NM_001146054.2		c.-25-466T>A		intron	N/A	NP_001139526.1	P37840-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCA	ENST00000618500.4	TSL:1	c.-57T>A		5_prime_UTR	Exon 1 of 5	ENSP00000484044.1	P37840-3
	SNCA	ENST00000394991.8	TSL:1 MANE Select	c.-25-466T>A		intron	N/A	ENSP00000378442.4	P37840-1
	SNCA	ENST00000394986.5	TSL:1	c.-25-466T>A		intron	N/A	ENSP00000378437.1	P37840-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151566 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 58228 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 30702

African (AFR) AF: 0.00 AC: 0 AN: 1600

American (AMR) AF: 0.00 AC: 0 AN: 3662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1348

East Asian (EAS) AF: 0.00 AC: 0 AN: 3304

South Asian (SAS) AF: 0.00 AC: 0 AN: 7892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 34982

Other (OTH) AF: 0.00 AC: 0 AN: 2968

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 151566 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 73956

African (AFR) AF: 0.00 AC: 0 AN: 41210

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5110

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67912

Other (OTH) AF: 0.00 AC: 0 AN: 2088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.97
DANN	Benign	0.77
PhyloP100		-0.88
PromoterAI		-0.14	Neutral

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: rs1372519; hg19: chr4-90757309;