chr5-122450972-G-C

Variant names:

• chr5-122450972-G-C
• rs55712196
• NM_005460.4:c.2125G>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001308100.2(SNCAIP):​c.2266G>C​(p.Glu756Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0118 in 1,614,162 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (10 hom., cov: 32)
  • Exomes 𝑓: 0.012 (135 hom.)
• Consequence: SNCAIP NM_001308100.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 6.85
• Publications: 16 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0047543645).
• BP6: Variant 5-122450972-G-C is Benign according to our data. Variant chr5-122450972-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 350498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 1239 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001308100.2. 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.2125G>C	p.Glu709Gln	missense	Exon 10 of 11	NP_005451.2
	SNCAIP	NM_001308100.2		c.2266G>C	p.Glu756Gln	missense	Exon 12 of 14	NP_001295029.1
	SNCAIP	NM_001308105.1		c.1945G>C	p.Glu649Gln	missense	Exon 8 of 9	NP_001295034.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNCAIP	ENST00000261368.13	TSL:1 MANE Select	c.2125G>C	p.Glu709Gln	missense	Exon 10 of 11	ENSP00000261368.8
	SNCAIP	ENST00000261367.11	TSL:1	c.2266G>C	p.Glu756Gln	missense	Exon 12 of 14	ENSP00000261367.7
	SNCAIP	ENST00000508017.5	TSL:1	n.*872G>C		non_coding_transcript_exon	Exon 8 of 9	ENSP00000424338.1

Frequencies

GnomAD3 genomes AF: 0.00815 AC: 1241 AN: 152184 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00870

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00806 AC: 2023 AN: 251030 AF XY: 0.00817

Gnomad AFR exome AF: 0.00203

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00929

Gnomad NFE exome AF: 0.0125

Gnomad OTH exome AF: 0.00784

GnomAD4 exome AF: 0.0121 AC: 17734 AN: 1461860 Hom.: 135 Cov.: 34 AF XY: 0.0120 AC XY: 8757 AN XY: 727228

African (AFR) AF: 0.00161 AC: 54 AN: 33480

American (AMR) AF: 0.00353 AC: 158 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00172 AC: 45 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00694 AC: 599 AN: 86258

European-Finnish (FIN) AF: 0.0106 AC: 566 AN: 53406

Middle Eastern (MID) AF: 0.00763 AC: 44 AN: 5768

European-Non Finnish (NFE) AF: 0.0141 AC: 15654 AN: 1112000

Other (OTH) AF: 0.0102 AC: 613 AN: 60392

GnomAD4 genome AF: 0.00814 AC: 1239 AN: 152302 Hom.: 10 Cov.: 32 AF XY: 0.00780 AC XY: 581 AN XY: 74458

African (AFR) AF: 0.00231 AC: 96 AN: 41558

American (AMR) AF: 0.00588 AC: 90 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00230 AC: 8 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00850 AC: 41 AN: 4824

European-Finnish (FIN) AF: 0.00952 AC: 101 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 880 AN: 68034

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0110 Hom.: 13

Bravo AF: 0.00750

TwinsUK AF: 0.0148 AC: 55

ALSPAC AF: 0.0143 AC: 55

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00813 AC: 987

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0124

EpiControl AF: 0.0111

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)
-	-	1	Parkinson Disease, Dominant/Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.80	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.9
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.70
MVP		0.77
MPC		0.76
ClinPred		0.0096	T
GERP RS		6.1
Varity_R		0.17
gMVP		0.26
Mutation Taster		=95/5	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: rs55712196; hg19: chr5-121786667; COSMIC: COSV54417015;