Variant 5-122422954-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005460.4(SNCAIP):c.217T>C(p.Phe73Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000243 in 1,614,182 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

SNCAIP
NM_005460.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.29

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012450457).

BP6

Variant 5-122422954-T-C is Benign according to our data. Variant chr5-122422954-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 730679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCAIP	NM_005460.4 linkuse as main transcript	c.217T>C	p.Phe73Leu	missense_variant	4/11	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.217T>C	p.Phe73Leu	missense_variant	4/11	1	NM_005460.4	ENSP00000261368	P1	Q9Y6H5-1

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

189

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000279

AC:

AN:

251206

Hom.:

AF XY:

0.000206

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.000173

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000138

AC:

202

AN:

1461852

Hom.:

Cov.:

AF XY:

0.000132

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00451

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152330

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00435

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.00122

ESP6500AA

AF:

0.00567

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000329

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;.;.;.;T;.

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D;D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.012

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

.;.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.2

D;D;D;N;N;N

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.030

D;D;D;T;T;T

Polyphen

1.0, 1.0, 0.98

.;.;.;D;D;D

Vest4

0.92, 0.90

MutPred

0.32

Loss of methylation at K72 (P = 0.0388);.;Loss of methylation at K72 (P = 0.0388);Loss of methylation at K72 (P = 0.0388);Loss of methylation at K72 (P = 0.0388);.;

MVP

0.68

MPC

0.82

ClinPred

0.098

GERP RS

5.7

Varity_R

0.56

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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