chr7-83075249-A-G

Variant names:

• chr7-83075249-A-G
• rs6950504
• NM_033026.6:c.3300+59001T>C

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+59001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 151,930 control chromosomes in the GnomAD database, including 17,811 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 0.48 (17811 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.488 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	NM_033026.6	MANE Select	c.3300+59001T>C		intron	N/A	NP_149015.2
	PCLO	NM_014510.3		c.3300+59001T>C		intron	N/A	NP_055325.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.3300+59001T>C		intron	N/A	ENSP00000334319.8
	PCLO	ENST00000423517.6	TSL:5	c.3300+59001T>C		intron	N/A	ENSP00000388393.2
	PCLO	ENST00000461143.1	TSL:2	n.361+59001T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73242 AN: 151812 Hom.: 17794 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.482 AC: 73299 AN: 151930 Hom.: 17811 Cov.: 32 AF XY: 0.484 AC XY: 35936 AN XY: 74230

African (AFR) AF: 0.483 AC: 20022 AN: 41436

American (AMR) AF: 0.498 AC: 7600 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1799 AN: 3464

East Asian (EAS) AF: 0.282 AC: 1454 AN: 5158

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4822

European-Finnish (FIN) AF: 0.507 AC: 5342 AN: 10546

Middle Eastern (MID) AF: 0.497 AC: 143 AN: 288

European-Non Finnish (NFE) AF: 0.487 AC: 33100 AN: 67928

Other (OTH) AF: 0.491 AC: 1033 AN: 2106

Alfa AF: 0.488 Hom.: 9589

Bravo AF: 0.479

Asia WGS AF: 0.399 AC: 1392 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.7
DANN	Benign	0.60
PhyloP100		1.1
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: rs6950504; hg19: chr7-82704565;