rs1418351789

Variant names:

• chr5-122312277-C-A
• rs1418351789
• NM_005460.4:c.-54C>A

Variant summary

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

The NM_005460.4(SNCAIP):​c.-54C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: SNCAIP NM_005460.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0150
• Publications: 0 publications found

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

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=-0.51).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005460.4. 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
	SNCAIP	NM_005460.4	MANE Select	c.-54C>A		5_prime_UTR	Exon 1 of 11	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.-1358C>A		5_prime_UTR	Exon 1 of 14	NP_001295029.1	Q9Y6H5-3
	SNCAIP	NM_001242935.3		c.-100C>A		5_prime_UTR	Exon 1 of 10	NP_001229864.1	Q9Y6H5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.-54C>A		5_prime_UTR	Exon 1 of 11	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.-1358C>A		5_prime_UTR	Exon 1 of 14	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000508017.5	TSL:1	n.-54C>A		non_coding_transcript_exon	Exon 1 of 9	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150942 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150942 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73654

African (AFR) AF: 0.0000243 AC: 1 AN: 41110

American (AMR) AF: 0.00 AC: 0 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 4956

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67672

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Parkinson Disease, Dominant/Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.1
DANN	Benign	0.78
PhyloP100		-0.015
PromoterAI		0.051	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: rs1418351789; hg19: chr5-121647972;