5-122460443-T-G

Position:

• chr5-122460443-T-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNCAIP	NM_005460.4	c.2755-3048T>G		intron_variant		ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13	c.2755-3048T>G		intron_variant		1	NM_005460.4	ENSP00000261368.8

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

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.256

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.215

Alfa AF: 0.188 Hom.: 631

Bravo AF: 0.234

Asia WGS AF: 0.266 AC: 922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.22
DANN	Benign	0.40

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: rs1841972; hg19: chr5-121796138;