5-122444650-C-T

Variant names:

• chr5-122444650-C-T
• rs113042472
• NM_005460.4:c.1510C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_005460.4(SNCAIP):​c.1510C>T​(p.Leu504Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00258 in 1,613,808 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (8 hom.)
• Consequence: SNCAIP NM_005460.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.62
• 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]

MGC32805 (HGNC:28478):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 5-122444650-C-T is Benign according to our data. Variant chr5-122444650-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 350495.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 225 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.1510C>T	p.Leu504Leu	synonymous	Exon 8 of 11	NP_005451.2	Q9Y6H5-1
	SNCAIP	NM_001308100.2		c.1651C>T	p.Leu551Leu	synonymous	Exon 10 of 14	NP_001295029.1	Q9Y6H5-3
	SNCAIP	NM_001308105.1		c.1330C>T	p.Leu444Leu	synonymous	Exon 6 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.1510C>T	p.Leu504Leu	synonymous	Exon 8 of 11	ENSP00000261368.8	Q9Y6H5-1
	SNCAIP	ENST00000261367.11	TSL:1	c.1651C>T	p.Leu551Leu	synonymous	Exon 10 of 14	ENSP00000261367.7	Q9Y6H5-3
	SNCAIP	ENST00000508017.5	TSL:1	n.*257C>T		non_coding_transcript_exon	Exon 6 of 9	ENSP00000424338.1	Q6L982

Frequencies

GnomAD3 genomes AF: 0.00148 AC: 225 AN: 152188 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.00145 AC: 365 AN: 251272 AF XY: 0.00155

Gnomad AFR exome AF: 0.000800

Gnomad AMR exome AF: 0.000838

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00233

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.00269 AC: 3936 AN: 1461504 Hom.: 8 Cov.: 31 AF XY: 0.00263 AC XY: 1912 AN XY: 727112

African (AFR) AF: 0.000538 AC: 18 AN: 33466

American (AMR) AF: 0.000760 AC: 34 AN: 44718

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00165 AC: 142 AN: 86246

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.00323 AC: 3586 AN: 1111672

Other (OTH) AF: 0.00248 AC: 150 AN: 60380

GnomAD4 genome AF: 0.00148 AC: 225 AN: 152304 Hom.: 2 Cov.: 32 AF XY: 0.00153 AC XY: 114 AN XY: 74472

African (AFR) AF: 0.000505 AC: 21 AN: 41580

American (AMR) AF: 0.00203 AC: 31 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00245 AC: 167 AN: 68034

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00196 Hom.: 0

Bravo AF: 0.00141

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Parkinson Disease, Dominant/Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		5.6
Mutation Taster		=97/3	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

dbSNP: rs113042472; hg19: chr5-121780345;