chr5-122444650-C-T

Variant names:

• chr5-122444650-C-T
• rs113042472
• NM_005460.4:c.1510C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_005460.4(SNCAIP):​c.1510C>T​(p.Leu504Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00258 in 1,613,808 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (8 hom.)
• Consequence: SNCAIP NM_005460.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.62

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]

MGC32805 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 5-122444650-C-T is Benign according to our data. Variant chr5-122444650-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 350495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 225 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4	c.1510C>T	p.Leu504Leu	synonymous_variant	Exon 8 of 11	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13	c.1510C>T	p.Leu504Leu	synonymous_variant	Exon 8 of 11	1	NM_005460.4	ENSP00000261368.8

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152188 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00145 AC: 365 AN: 251272 Hom.: 2 AF XY: 0.00155 AC XY: 211 AN XY: 135796

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00173

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00269 AC: 3936 AN: 1461504 Hom.: 8 Cov.: 31 AF XY: 0.00263 AC XY: 1912 AN XY: 727112

Gnomad4 AFR exome AF: 0.000538

Gnomad4 AMR exome AF: 0.000760

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00165

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00323

Gnomad4 OTH exome AF: 0.00248

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74472

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00245

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00196 Hom.: 0

Bravo AF: 0.00141

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 06, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Parkinson Disease, Dominant/Recessive Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs113042472; hg19: chr5-121780345;