chr5-122450708-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005460.4(SNCAIP):c.1861C>T(p.Arg621Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00441 in 1,614,158 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R621H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 20 hom. )

Consequence

SNCAIP
NM_005460.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts U:1B:4

Conservation

PhyloP100: 5.33

Publications

32 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:

MGC32805 (HGNC:28478):

MGC32805 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010618597).

BP6

Variant 5-122450708-C-T is Benign according to our data. Variant chr5-122450708-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 6078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 454 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNCAIP	NM_005460.4	MANE Select	c.1861C>T	p.Arg621Cys	missense	Exon 10 of 11	NP_005451.2	Q9Y6H5-1
SNCAIP	NM_001308100.2		c.2002C>T	p.Arg668Cys	missense	Exon 12 of 14	NP_001295029.1	Q9Y6H5-3
SNCAIP	NM_001308105.1		c.1681C>T	p.Arg561Cys	missense	Exon 8 of 9	NP_001295034.1	B7Z995

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.1861C>T	p.Arg621Cys	missense	Exon 10 of 11	ENSP00000261368.8	Q9Y6H5-1
SNCAIP	ENST00000261367.11	TSL:1	c.2002C>T	p.Arg668Cys	missense	Exon 12 of 14	ENSP00000261367.7	Q9Y6H5-3
SNCAIP	ENST00000508017.5	TSL:1	n.*608C>T		non_coding_transcript_exon	Exon 8 of 9	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes

AF:

0.00298

AC:

454

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00499

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00510

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00334

AC:

838

AN:

251172

AF XY:

0.00350

show subpopulations

Gnomad AFR exome

AF:

0.000496

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00628

Gnomad NFE exome

AF:

0.00546

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00456

AC:

6664

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00449

AC XY:

3266

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33480

American (AMR)

AF:

0.000939

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00149

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.000336

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00627

AC:

335

AN:

53418

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00529

AC:

5887

AN:

1111976

Other (OTH)

AF:

0.00465

AC:

281

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

391

782

1172

1563

1954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

210

420

630

840

1050

<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:

0.00298

AC:

454

AN:

152304

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000698

AC:

AN:

41564

American (AMR)

AF:

0.000915

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00499

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00510

AC:

347

AN:

68030

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00438

Hom.:

Bravo

AF:

0.00280

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00361

AC:

438

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00575

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Parkinson Disease, Dominant/Recessive (1)

Parkinson disease, late-onset (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.031

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

PhyloP100

5.3

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Benign

0.079

Polyphen

1.0

Vest4

0.87

MVP

0.75

MPC

0.90

ClinPred

0.029

GERP RS

6.1

Varity_R

0.41

gMVP

0.43

Mutation Taster

=81/19

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over