rs2242224

Variant names:

• chr5-122425326-G-A
• rs2242224
• NM_005460.4:c.1003-26G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-122425326-G-A
• chr5-122425326-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005460.4(SNCAIP):​c.1003-26G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,592,538 control chromosomes in the GnomAD database, including 48,390 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 0.22 (4034 hom., cov: 33)
  • Exomes 𝑓: 0.24 (44356 hom.)
• Consequence: SNCAIP NM_005460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

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.1003-26G>A		intron	N/A	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.1144-26G>A		intron	N/A	NP_001295029.1	Q9Y6H5-3
	SNCAIP	NM_001308105.1		c.1002+1587G>A		intron	N/A	NP_001295034.1	B7Z995

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.1003-26G>A		intron	N/A	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.1144-26G>A		intron	N/A	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000508017.5	TSL:1	n.131-6643G>A		intron	N/A	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32749 AN: 152030 Hom.: 4026 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.205

GnomAD2 exomes AF: 0.254 AC: 63549 AN: 250226 AF XY: 0.257

Gnomad AFR exome AF: 0.0961

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.267

Gnomad FIN exome AF: 0.327

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.254

GnomAD4 exome AF: 0.244 AC: 351070 AN: 1440390 Hom.: 44356 Cov.: 28 AF XY: 0.246 AC XY: 176916 AN XY: 717958

African (AFR) AF: 0.0931 AC: 3082 AN: 33114

American (AMR) AF: 0.260 AC: 11629 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 5045 AN: 26006

East Asian (EAS) AF: 0.258 AC: 10233 AN: 39598

South Asian (SAS) AF: 0.305 AC: 26151 AN: 85724

European-Finnish (FIN) AF: 0.332 AC: 17689 AN: 53340

Middle Eastern (MID) AF: 0.204 AC: 1169 AN: 5726

European-Non Finnish (NFE) AF: 0.240 AC: 262004 AN: 1092504

Other (OTH) AF: 0.236 AC: 14068 AN: 59682

GnomAD4 genome AF: 0.215 AC: 32772 AN: 152148 Hom.: 4034 Cov.: 33 AF XY: 0.221 AC XY: 16403 AN XY: 74378

African (AFR) AF: 0.103 AC: 4289 AN: 41524

American (AMR) AF: 0.241 AC: 3688 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 680 AN: 3472

East Asian (EAS) AF: 0.274 AC: 1417 AN: 5178

South Asian (SAS) AF: 0.320 AC: 1539 AN: 4814

European-Finnish (FIN) AF: 0.327 AC: 3461 AN: 10570

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16937 AN: 67978

Other (OTH) AF: 0.205 AC: 434 AN: 2116

Alfa AF: 0.227 Hom.: 1329

Bravo AF: 0.200

Asia WGS AF: 0.262 AC: 909 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.42
DANN	Benign	0.76
PhyloP100		-0.35
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2242224; hg19: chr5-121761021;