5-122312282-C-G

Variant names:

• chr5-122312282-C-G
• rs192969505
• NM_005460.4:c.-49C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005460.4(SNCAIP):​c.-49C>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00847 in 150,694 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0085 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SNCAIP NM_005460.4 splice_region
• Scores: Splicing: ADA: 0.004837
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.552
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 5-122312282-C-G is Benign according to our data. Variant chr5-122312282-C-G is described in ClinVar as Benign. ClinVar VariationId is 350479.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00847 (1277/150694) while in subpopulation AFR AF = 0.0288 (1184/41122). AF 95% confidence interval is 0.0274. There are 12 homozygotes in GnomAd4. There are 614 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1277 AD gene.

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.-49C>G		splice_region	Exon 1 of 11	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_005460.4	MANE Select	c.-49C>G		5_prime_UTR	Exon 1 of 11	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.-1353C>G		splice_region	Exon 1 of 14	NP_001295029.1	Q9Y6H5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.-49C>G		splice_region	Exon 1 of 11	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.-1353C>G		splice_region	Exon 1 of 14	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.-49C>G		5_prime_UTR	Exon 1 of 11	ENSP00000261368.8	Q9Y6H5-1

Frequencies

GnomAD3 genomes AF: 0.00845 AC: 1273 AN: 150578 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000563

Gnomad OTH AF: 0.00630

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 196 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 156

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 180

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.00847 AC: 1277 AN: 150694 Hom.: 12 Cov.: 32 AF XY: 0.00835 AC XY: 614 AN XY: 73572

African (AFR) AF: 0.0288 AC: 1184 AN: 41122

American (AMR) AF: 0.00263 AC: 40 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 4894

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.000563 AC: 38 AN: 67538

Other (OTH) AF: 0.00671 AC: 14 AN: 2086

Alfa AF: 0.000107 Hom.: 0

Bravo AF: 0.00947

Asia WGS AF: 0.00289 AC: 10 AN: 3472

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Parkinson Disease, Dominant/Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.8
DANN	Benign	0.76
PhyloP100		-0.55
PromoterAI		-0.047	Neutral
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0048
dbscSNV1_RF	Benign	0.096
SpliceAI score (max)		0.050		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: rs192969505; hg19: chr5-121647977;