5-122403839-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNCAIP	NM_005460.4	c.104G>A	p.Cys35Tyr	missense_variant	Exon 3 of 11	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13	c.104G>A	p.Cys35Tyr	missense_variant	Exon 3 of 11	1	NM_005460.4	ENSP00000261368.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.104G>A (p.C35Y) alteration is located in exon 3 (coding exon 2) of the SNCAIP gene. This alteration results from a G to A substitution at nucleotide position 104, causing the cysteine (C) at amino acid position 35 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.60	D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.0	.;.;.;.;M;.;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-8.1	D;D;D;N;N;.;N;.;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0040	D;D;D;D;D;.;D;.;D
Sift4G	Benign	0.34	T;T;T;T;T;D;T;T;T
Polyphen		0.99, 0.99, 0.99	.;.;.;D;D;.;D;.;.
Vest4		0.88, 0.64, 0.93, 0.83, 0.53
MutPred		0.46		Gain of helix (P = 0.027);.;Gain of helix (P = 0.027);Gain of helix (P = 0.027);Gain of helix (P = 0.027);.;.;Gain of helix (P = 0.027);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-121739534;