5-122403816-G-A

Position:

chr5-122403816-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005460.4(SNCAIP):c.81G>A(p.Thr27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,684 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 48 hom. )

Consequence

SNCAIP
NM_005460.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.357

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058555007).

BP6

Variant 5-122403816-G-A is Benign according to our data. Variant chr5-122403816-G-A is described in ClinVar as [Benign]. Clinvar id is 350482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.357 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0017 (259/152110) while in subpopulation SAS AF= 0.0201 (97/4818). AF 95% confidence interval is 0.0169. There are 1 homozygotes in gnomad4. There are 157 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCAIP	NM_005460.4 linkuse as main transcript	c.81G>A	p.Thr27=	synonymous_variant	3/11	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13 linkuse as main transcript	c.81G>A	p.Thr27=	synonymous_variant	3/11	1	NM_005460.4	ENSP00000261368	P1	Q9Y6H5-1

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

258

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000721

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00420

AC:

1056

AN:

251160

Hom.:

AF XY:

0.00511

AC XY:

694

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0211

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00258

AC:

3765

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00318

AC XY:

2309

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0209

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.00368

GnomAD4 genome

AF:

0.00170

AC:

259

AN:

152110

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

157

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00257

Hom.:

Bravo

AF:

0.00147

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00174

AC:

ExAC

AF:

0.00456

AC:

553

Asia WGS

AF:

0.00693

AC:

AN:

3476

EpiCase

AF:

0.00185

EpiControl

AF:

0.00184

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinson Disease, Dominant/Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N;N

PROVEAN

Benign

0.42

REVEL

Benign

0.10

Sift

Benign

0.28

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.16

MVP

0.21

ClinPred

0.0039

GERP RS

3.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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