5-122422967-A-G

Variant names:

• chr5-122422967-A-G
• NM_005460.4:c.230A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005460.4(SNCAIP):​c.230A>G​(p.Lys77Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 8.49

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.230A>G	p.Lys77Arg	missense_variant	Exon 4 of 11	ENST00000261368.13	NP_005451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNCAIP	ENST00000261368.13	c.230A>G	p.Lys77Arg	missense_variant	Exon 4 of 11	1	NM_005460.4	ENSP00000261368.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230A>G (p.K77R) alteration is located in exon 4 (coding exon 3) of the SNCAIP gene. This alteration results from a A to G substitution at nucleotide position 230, causing the lysine (K) at amino acid position 77 to be replaced by an arginine (R). 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	Uncertain	0.39
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	.;.;.;.;T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.1	.;.;.;.;M;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-2.2	N;N;N;N;N;N
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D;D;D;D;D
Sift4G	Benign	0.13	T;T;T;T;T;T
Polyphen		1.0, 1.0, 0.99	.;.;.;D;D;D
Vest4		0.81, 0.83
MutPred		0.27		Loss of methylation at K77 (P = 0.0042);.;Loss of methylation at K77 (P = 0.0042);Loss of methylation at K77 (P = 0.0042);Loss of methylation at K77 (P = 0.0042);.;
MVP		0.78
MPC		0.69
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.47
gMVP		0.43

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: chr5-121758662;