NM_005460.4:c.1571A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005460.4(SNCAIP):ā€‹c.1571A>Gā€‹(p.Lys524Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,784 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

SNCAIP
NM_005460.4 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.19
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 Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNCAIPNM_005460.4 linkc.1571A>G p.Lys524Arg missense_variant Exon 8 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.1571A>G p.Lys524Arg missense_variant Exon 8 of 11 1 NM_005460.4 ENSP00000261368.8 Q9Y6H5-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461650
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727148
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74322
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1571A>G (p.K524R) alteration is located in exon 8 (coding exon 7) of the SNCAIP gene. This alteration results from a A to G substitution at nucleotide position 1571, causing the lysine (K) at amino acid position 524 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;T;.;.
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.68
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.1
.;M;.;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.3
N;N;N;N
REVEL
Uncertain
0.43
Sift
Uncertain
0.0090
D;D;D;D
Sift4G
Uncertain
0.036
D;T;T;T
Polyphen
0.99
D;D;D;D
Vest4
0.64, 0.47, 0.60
MutPred
0.35
.;Loss of methylation at K524 (P = 0.0099);.;.;
MVP
0.75
MPC
0.69
ClinPred
0.96
D
GERP RS
5.6
Varity_R
0.43
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs769298110; hg19: chr5-121780406; API