5-122446816-G-T

Variant names:

• chr5-122446816-G-T
• rs3811876
• NM_005460.4:c.1592+2084G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001308100.2(SNCAIP):​c.1733+2084G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0501 in 152,252 control chromosomes in the GnomAD database, including 256 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.050 (256 hom., cov: 32)
• Consequence: SNCAIP NM_001308100.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 2 publications found

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:28478):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308100.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	NM_005460.4	MANE Select	c.1592+2084G>T		intron	N/A	NP_005451.2
	SNCAIP	NM_001308100.2		c.1733+2084G>T		intron	N/A	NP_001295029.1
	SNCAIP	NM_001308105.1		c.1412+2084G>T		intron	N/A	NP_001295034.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.1592+2084G>T		intron	N/A	ENSP00000261368.8
	SNCAIP	ENST00000261367.11	TSL:1	c.1733+2084G>T		intron	N/A	ENSP00000261367.7
	SNCAIP	ENST00000508017.5	TSL:1	n.*339+2084G>T		intron	N/A	ENSP00000424338.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7636 AN: 152134 Hom.: 256 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0457

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.0468

Gnomad OTH AF: 0.0622

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0501 AC: 7631 AN: 152252 Hom.: 256 Cov.: 32 AF XY: 0.0495 AC XY: 3688 AN XY: 74448

African (AFR) AF: 0.0470 AC: 1952 AN: 41536

American (AMR) AF: 0.0457 AC: 699 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0894 AC: 310 AN: 3468

East Asian (EAS) AF: 0.166 AC: 857 AN: 5172

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4830

European-Finnish (FIN) AF: 0.0318 AC: 337 AN: 10610

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.0468 AC: 3185 AN: 68012

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0478 Hom.: 175

Bravo AF: 0.0525

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.55
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3811876; hg19: chr5-121782511;