rs12136063

Positions:

• chr1-109471548-G-A
• chr1-109471548-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040709.2(SYPL2):​c.130-4033G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,668 control chromosomes in the GnomAD database, including 30,845 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (30845 hom., cov: 31)
• Consequence: SYPL2 NM_001040709.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

Genes affected

SYPL2 (HGNC:27638): (synaptophysin like 2) Involved in substantia nigra development. Predicted to be integral component of membrane. Predicted to be active in synaptic vesicle membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYPL2	NM_001040709.2	c.130-4033G>A		intron_variant		ENST00000369872.4	NP_001035799.1
SYPL2	XM_011541283.3	c.130-4033G>A		intron_variant			XP_011539585.1
SYPL2	XM_011541284.3	c.130-4033G>A		intron_variant			XP_011539586.1
SYPL2	XM_011541285.2	c.130-4033G>A		intron_variant			XP_011539587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYPL2	ENST00000369872.4	c.130-4033G>A		intron_variant		1	NM_001040709.2	ENSP00000358888.3

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92417 AN: 151550 Hom.: 30828 Cov.: 31

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.760

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.958

Gnomad SAS AF: 0.725

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.670

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.610 AC: 92451 AN: 151668 Hom.: 30845 Cov.: 31 AF XY: 0.613 AC XY: 45427 AN XY: 74096

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.761

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.958

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.673

Alfa AF: 0.695 Hom.: 37487

Bravo AF: 0.610

Asia WGS AF: 0.790 AC: 2744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.73

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

LitVar

Other links and lift over

dbSNP: rs12136063; hg19: chr1-110014170;