5-122460443-T-G

Variant names:

• chr5-122460443-T-G
• rs1841972
• NM_005460.4:c.2755-3048T>G

Variant summary

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

The NM_005460.4(SNCAIP):​c.2755-3048T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,084 control chromosomes in the GnomAD database, including 4,545 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 0.24 (4545 hom., cov: 32)
• Consequence: SNCAIP NM_005460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.954
• Publications: 4 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):

LOC107986446 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005460.4. 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.2755-3048T>G		intron	N/A	NP_005451.2
	SNCAIP	NM_001308100.2		c.2967-3048T>G		intron	N/A	NP_001295029.1
	SNCAIP	NM_001308105.1		c.2575-3048T>G		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.2755-3048T>G		intron	N/A	ENSP00000261368.8
	SNCAIP	ENST00000261367.11	TSL:1	c.2967-3048T>G		intron	N/A	ENSP00000261367.7
	SNCAIP	ENST00000508017.5	TSL:1	n.*1502-3048T>G		intron	N/A	ENSP00000424338.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36539 AN: 151966 Hom.: 4529 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.241 AC: 36600 AN: 152084 Hom.: 4545 Cov.: 32 AF XY: 0.244 AC XY: 18106 AN XY: 74328

African (AFR) AF: 0.254 AC: 10542 AN: 41474

American (AMR) AF: 0.224 AC: 3417 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3466

East Asian (EAS) AF: 0.256 AC: 1325 AN: 5166

South Asian (SAS) AF: 0.299 AC: 1437 AN: 4810

European-Finnish (FIN) AF: 0.286 AC: 3032 AN: 10588

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15482 AN: 67986

Other (OTH) AF: 0.215 AC: 455 AN: 2116

Alfa AF: 0.212 Hom.: 1370

Bravo AF: 0.234

Asia WGS AF: 0.266 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.40
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1841972; hg19: chr5-121796138;