NM_005460.4:c.1816C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005460.4(SNCAIP):​c.1816C>T​(p.Arg606Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

SNCAIP
NM_005460.4 missense

Scores

2
6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23869824).
BS2
High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNCAIPNM_005460.4 linkc.1816C>T p.Arg606Trp 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.1816C>T p.Arg606Trp missense_variant Exon 10 of 11 1 NM_005460.4 ENSP00000261368.8 Q9Y6H5-1

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000917
AC:
23
AN:
250706
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135796
show subpopulations
Gnomad AFR exome
AF:
0.0000631
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000705
AC:
103
AN:
1461844
Hom.:
0
Cov.:
33
AF XY:
0.0000784
AC XY:
57
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000246
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:
0.0000764
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152168
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000165
Hom.:
0
Bravo
AF:
0.000132
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000906
AC:
11
EpiCase
AF:
0.000109
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 05, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1816C>T (p.R606W) alteration is located in exon 10 (coding exon 9) of the SNCAIP gene. This alteration results from a C to T substitution at nucleotide position 1816, causing the arginine (R) at amino acid position 606 to be replaced by a tryptophan (W). 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
Benign
0.12
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.26
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.10
.;T;.;.
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.90
D;D;D;D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.24
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
.;L;.;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-2.0
N;N;N;N
REVEL
Benign
0.16
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Uncertain
0.022
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.59, 0.59, 0.59
MVP
0.75
MPC
0.70
ClinPred
0.25
T
GERP RS
4.2
Varity_R
0.18
gMVP
0.28

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: rs201736134; hg19: chr5-121786358; COSMIC: COSV54412227; API