rs10487656

Positions:

• chr7-83070785-T-C

Variant summary

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

The NM_033026.6(PCLO):​c.3300+63465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,052 control chromosomes in the GnomAD database, including 4,811 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 0.24 (4811 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

Genes affected

PCLO (HGNC:13406): (piccolo presynaptic cytomatrix protein) The protein encoded by this gene is part of the presynaptic cytoskeletal matrix, which is involved in establishing active synaptic zones and in synaptic vesicle trafficking. Variations in this gene have been associated with bipolar disorder and major depressive disorder. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCLO	NM_033026.6	c.3300+63465A>G		intron_variant		ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.3300+63465A>G		intron_variant		2	NM_033026.6	ENSP00000334319	P1
PCLO	ENST00000423517.6	c.3300+63465A>G		intron_variant		5		ENSP00000388393
PCLO	ENST00000461143.1	n.361+63465A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35788 AN: 151936 Hom.: 4801 Cov.: 32

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.295

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.236 AC: 35844 AN: 152052 Hom.: 4811 Cov.: 32 AF XY: 0.240 AC XY: 17856 AN XY: 74352

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.235

Alfa AF: 0.199 Hom.: 444

Bravo AF: 0.248

Asia WGS AF: 0.423 AC: 1466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.19
DANN	Benign	0.89

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: rs10487656; hg19: chr7-82700101;