5-122440031-G-T

Variant names:

• chr5-122440031-G-T
• rs10519701
• NM_005460.4:c.1297-598G>T

Variant summary

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

The NM_005460.4(SNCAIP):​c.1297-598G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 152,190 control chromosomes in the GnomAD database, including 226 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 0.040 (226 hom., cov: 33)
• Consequence: SNCAIP NM_005460.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0869 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	NM_005460.4	MANE Select	c.1297-598G>T		intron	N/A	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.1438-598G>T		intron	N/A	NP_001295029.1	Q9Y6H5-3
	SNCAIP	NM_001308105.1		c.1117-598G>T		intron	N/A	NP_001295034.1	B7Z995

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.1297-598G>T		intron	N/A	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.1438-598G>T		intron	N/A	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000508017.5	TSL:1	n.*44-598G>T		intron	N/A	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes AF: 0.0402 AC: 6109 AN: 152072 Hom.: 225 Cov.: 33

Gnomad AFR AF: 0.0894

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0614

Gnomad ASJ AF: 0.00837

Gnomad EAS AF: 0.0903

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.0216

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00642

Gnomad OTH AF: 0.0315

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

GnomAD4 genome AF: 0.0402 AC: 6116 AN: 152190 Hom.: 226 Cov.: 33 AF XY: 0.0419 AC XY: 3116 AN XY: 74400

African (AFR) AF: 0.0893 AC: 3708 AN: 41506

American (AMR) AF: 0.0612 AC: 936 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00837 AC: 29 AN: 3466

East Asian (EAS) AF: 0.0909 AC: 472 AN: 5190

South Asian (SAS) AF: 0.0494 AC: 238 AN: 4816

European-Finnish (FIN) AF: 0.0216 AC: 229 AN: 10582

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00643 AC: 437 AN: 68008

Other (OTH) AF: 0.0307 AC: 65 AN: 2114

Alfa AF: 0.0250 Hom.: 39

Bravo AF: 0.0452

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		1.8
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: rs10519701; hg19: chr5-121775726;