7-83096302-G-C

Variant names:

• chr7-83096302-G-C
• rs6947662
• NM_033026.6:c.3300+37948C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033026.6(PCLO):​c.3300+37948C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,790 control chromosomes in the GnomAD database, including 16,418 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 0.46 (16418 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386
• Publications: 2 publications found

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]

PCLO Gene-Disease associations (from GenCC):

• pontocerebellar hypoplasia type 3

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033026.6. 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
	PCLO	NM_033026.6	MANE Select	c.3300+37948C>G		intron	N/A	NP_149015.2	Q9Y6V0-5
	PCLO	NM_014510.3		c.3300+37948C>G		intron	N/A	NP_055325.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.3300+37948C>G		intron	N/A	ENSP00000334319.8	Q9Y6V0-5
	PCLO	ENST00000423517.6	TSL:5	c.3300+37948C>G		intron	N/A	ENSP00000388393.2	Q9Y6V0-6
	PCLO	ENST00000461143.1	TSL:2	n.361+37948C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69635 AN: 151672 Hom.: 16394 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.408

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.346

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.459 AC: 69711 AN: 151790 Hom.: 16418 Cov.: 31 AF XY: 0.467 AC XY: 34601 AN XY: 74148

African (AFR) AF: 0.479 AC: 19826 AN: 41406

American (AMR) AF: 0.542 AC: 8262 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3464

East Asian (EAS) AF: 0.712 AC: 3665 AN: 5150

South Asian (SAS) AF: 0.407 AC: 1962 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5428 AN: 10506

Middle Eastern (MID) AF: 0.331 AC: 96 AN: 290

European-Non Finnish (NFE) AF: 0.409 AC: 27774 AN: 67888

Other (OTH) AF: 0.484 AC: 1020 AN: 2106

Alfa AF: 0.272 Hom.: 612

Bravo AF: 0.466

Asia WGS AF: 0.586 AC: 2037 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.60
DANN	Benign	0.76
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

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: rs6947662; hg19: chr7-82725618;