rs304383

Variant names:

• chr5-122425719-A-C
• rs304383
• NM_005460.4:c.1182+188A>C

Variant summary

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

The NM_005460.4(SNCAIP):​c.1182+188A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,088 control chromosomes in the GnomAD database, including 9,701 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 0.35 (9701 hom., cov: 33)
• Consequence: SNCAIP NM_005460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.76

Genes affected

SNCAIP (HGNC:11139): (synuclein alpha interacting protein) This gene encodes a protein containing several protein-protein interaction domains, including ankyrin-like repeats, a coiled-coil domain, and an ATP/GTP-binding motif. The encoded protein interacts with alpha-synuclein in neuronal tissue and may play a role in the formation of cytoplasmic inclusions and neurodegeneration. A mutation in this gene has been associated with Parkinson's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4	c.1182+188A>C		intron_variant	Intron 5 of 10	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13	c.1182+188A>C		intron_variant	Intron 5 of 10	1	NM_005460.4	ENSP00000261368.8

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52671 AN: 151970 Hom.: 9693 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0651

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.354

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52707 AN: 152088 Hom.: 9701 Cov.: 33 AF XY: 0.337 AC XY: 25088 AN XY: 74352

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.352

Alfa AF: 0.350 Hom.: 5301

Bravo AF: 0.351

Asia WGS AF: 0.169 AC: 590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.058
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs304383; hg19: chr5-121761414;