5-122450708-C-T

Position:

chr5-122450708-C-T

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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:):

MGC32805 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 6078.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-122450708-C-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 454 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCAIP	NM_005460.4 linkuse as main transcript	c.1861C>T	p.Arg621Cys	missense_variant	10/11	ENST00000261368.13	NP_005451.2	Q9Y6H5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13 linkuse as main transcript	c.1861C>T	p.Arg621Cys	missense_variant	10/11	1	NM_005460.4	ENSP00000261368.8		Q9Y6H5-1

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

GnomAD3 exomes

AF:

0.00334

AC:

838

AN:

251172

Hom.:

AF XY:

0.00350

AC XY:

475

AN XY:

135848

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 SAS exome

AF:

0.000294

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

Gnomad4 AFR exome

AF:

0.000687

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00149

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.00627

Gnomad4 NFE exome

AF:

0.00529

Gnomad4 OTH exome

AF:

0.00465

GnomAD4 genome

AF:

0.00298

AC:

454

AN:

152304

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00499

Gnomad4 NFE

AF:

0.00510

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00405

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

Significance: Likely benign

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	MGC32805: BS2; SNCAIP: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Parkinson disease, late-onset

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

OMIM

Mar 21, 2008

- -

Parkinson Disease, Dominant/Recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

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

Uncertain

0.40

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Uncertain

0.11

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

.;T;.;.

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Benign

0.031

MetaRNN

Benign

0.011

T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

.;M;.;.

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.079

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.87, 0.92, 0.87

MVP

0.75

MPC

0.90

ClinPred

0.029

GERP RS

6.1

Varity_R

0.41

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over