rs767723638

Variant names:

• chr5-122422903-C-G
• rs767723638
• NM_005460.4:c.166C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-122422903-C-G
• chr5-122422903-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005460.4(SNCAIP):​c.166C>G​(p.Leu56Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L56F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SNCAIP NM_005460.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.02
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33083037).

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.166C>G	p.Leu56Val	missense	Exon 4 of 11	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.307C>G	p.Leu103Val	missense	Exon 6 of 14	NP_001295029.1	Q9Y6H5-3
	SNCAIP	NM_001308105.1		c.166C>G	p.Leu56Val	missense	Exon 3 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.166C>G	p.Leu56Val	missense	Exon 4 of 11	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.307C>G	p.Leu103Val	missense	Exon 6 of 14	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000510003.5	TSL:1	n.260C>G		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251064 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461722 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727182

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111878

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Uncertain	0.013	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		7.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.20
Sift	Benign	0.058	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.15		Gain of glycosylation at S54 (P = 0.1502)
MVP		0.76
MPC		0.77
ClinPred		0.90	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.14
Mutation Taster		=15/85	disease causing

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: rs767723638; hg19: chr5-121758598;