dbSNP rs2242224: SNCAIP:c.1003-26G>A (chr5-122425326-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.347

Publications

8 publications found

Variant links:

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]

SNCAIP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4 link	c.1003-26G>A		intron_variant	Intron 4 of 10	ENST00000261368.13	NP_005451.2	Q9Y6H5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13 link	c.1003-26G>A		intron_variant	Intron 4 of 10	1	NM_005460.4	ENSP00000261368.8		Q9Y6H5-1

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32749

AN:

152030

Hom.:

4026

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.246

AC XY:

176916

AN XY:

717958

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

11662

23324

34986

46648

58310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8754

17508

26262

35016

43770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.215

AC:

32772

AN:

152148

Hom.:

4034

Cov.:

AF XY:

0.221

AC XY:

16403

AN XY:

74378

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.249

AC:

16937

AN:

67978

Other (OTH)

AF:

0.205

AC:

434

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1297

2594

3892

5189

6486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.42

(source)

DANN

Benign

0.76

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over