5-122403839-G-A

Variant names:

• chr5-122403839-G-A
• NM_005460.4:c.104G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005460.4(SNCAIP):​c.104G>A​(p.Cys35Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNCAIP NM_005460.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.104G>A	p.Cys35Tyr	missense	Exon 3 of 11	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.245G>A	p.Cys82Tyr	missense	Exon 5 of 14	NP_001295029.1	Q9Y6H5-3
	SNCAIP	NM_001308105.1		c.104G>A	p.Cys35Tyr	missense	Exon 2 of 9	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.104G>A	p.Cys35Tyr	missense	Exon 3 of 11	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.245G>A	p.Cys82Tyr	missense	Exon 5 of 14	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000508017.5	TSL:1	n.104G>A		non_coding_transcript_exon	Exon 3 of 9	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.4
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.1	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.34	T
Polyphen		0.99	D
Vest4		0.88
MutPred		0.46		Gain of helix (P = 0.027)
MVP		0.83
MPC		1.0
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.61
gMVP		0.26
Mutation Taster		=69/31	polymorphism

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

hg19: chr5-121739534;