rs144492699

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005460.4(SNCAIP):​c.1817G>A​(p.Arg606Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000592 in 1,614,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 1 hom. )

Consequence

SNCAIP
NM_005460.4 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.04113114).
BS2
High AC in GnomAd4 at 61 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNCAIPNM_005460.4 linkc.1817G>A p.Arg606Gln missense_variant Exon 10 of 11 ENST00000261368.13 NP_005451.2 Q9Y6H5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNCAIPENST00000261368.13 linkc.1817G>A p.Arg606Gln missense_variant Exon 10 of 11 1 NM_005460.4 ENSP00000261368.8 Q9Y6H5-1

Frequencies

GnomAD3 genomes
AF:
0.000401
AC:
61
AN:
152118
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000706
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000479
AC:
120
AN:
250726
Hom.:
0
AF XY:
0.000501
AC XY:
68
AN XY:
135790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000376
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000899
Gnomad OTH exome
AF:
0.000328
GnomAD4 exome
AF:
0.000612
AC:
894
AN:
1461820
Hom.:
1
Cov.:
33
AF XY:
0.000637
AC XY:
463
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000358
Gnomad4 ASJ exome
AF:
0.000153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000762
Gnomad4 OTH exome
AF:
0.000331
GnomAD4 genome
AF:
0.000401
AC:
61
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.000336
AC XY:
25
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.000589
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000706
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000770
Hom.:
0
Bravo
AF:
0.000370
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000698
AC:
6
ExAC
AF:
0.000552
AC:
67
EpiCase
AF:
0.000818
EpiControl
AF:
0.000830

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Parkinson Disease, Dominant/Recessive Uncertain:1
Apr 28, 2017
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
23
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.045
.;T;.;.
Eigen
Benign
0.14
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D;D;D;D
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.041
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L;.;.
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.67
N;N;N;N
REVEL
Benign
0.071
Sift
Uncertain
0.0030
D;D;D;D
Sift4G
Benign
0.30
T;T;T;T
Polyphen
0.80
P;B;P;D
Vest4
0.26, 0.21, 0.28
MVP
0.66
MPC
0.63
ClinPred
0.13
T
GERP RS
5.2
Varity_R
0.13
gMVP
0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144492699; hg19: chr5-121786359; COSMIC: COSV54407091; API