rs55712196

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.2125G>C(p.Glu709Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0118 in 1,614,162 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0081 ( 10 hom., cov: 32)

Exomes 𝑓: 0.012 ( 135 hom. )

Consequence

SNCAIP
NM_005460.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 6.85

Publications

16 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=0.0047543645).

BP6

Variant 5-122450972-G-C is Benign according to our data. Variant chr5-122450972-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 350498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1239 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4 link	c.2125G>C	p.Glu709Gln	missense_variant	Exon 10 of 11	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13 link	c.2125G>C	p.Glu709Gln	missense_variant	Exon 10 of 11	1	NM_005460.4	ENSP00000261368.8

Frequencies

GnomAD3 genomes

AF:

0.00815

AC:

1241

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00870

Gnomad FIN

AF:

0.00952

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00806

AC:

2023

AN:

251030

AF XY:

0.00817

show subpopulations

Gnomad AFR exome

AF:

0.00203

Gnomad AMR exome

AF:

0.00347

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00929

Gnomad NFE exome

AF:

0.0125

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.0121

AC:

17734

AN:

1461860

Hom.:

135

Cov.:

AF XY:

0.0120

AC XY:

8757

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

33480

American (AMR)

AF:

0.00353

AC:

158

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00694

AC:

599

AN:

86258

European-Finnish (FIN)

AF:

0.0106

AC:

566

AN:

53406

Middle Eastern (MID)

AF:

0.00763

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0141

AC:

15654

AN:

1112000

Other (OTH)

AF:

0.0102

AC:

613

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1089

2178

3267

4356

5445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.00814

AC:

1239

AN:

152302

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

581

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41558

American (AMR)

AF:

0.00588

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00850

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00952

AC:

101

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

880

AN:

68034

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0110

Hom.:

Bravo

AF:

0.00750

TwinsUK

AF:

0.0148

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00813

AC:

987

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0124

EpiControl

AF:

0.0111

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SNCAIP: BP4, BS1, BS2 -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in ESP (all): 103/13006=0.79%; Frequency in ESP (EA): 94/8600=1.09% -

Parkinson Disease, Dominant/Recessive

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;.;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.80

T;T;T;T

MetaRNN

Benign

0.0048

T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.1

.;M;.;.

PhyloP100

6.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0020

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.70, 0.70, 0.73

MVP

0.77

MPC

0.76

ClinPred

0.0096

GERP RS

6.1

Varity_R

0.17

gMVP

0.26

Mutation Taster

=95/5

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over