7-83016894-T-C

Variant names:

• chr7-83016894-T-C
• rs28156
• NM_033026.6:c.3301-50407A>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.3301-50407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 151,934 control chromosomes in the GnomAD database, including 19,643 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 (19643 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.3301-50407A>G		intron_variant	Intron 3 of 24	ENST00000333891.14	NP_149015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.3301-50407A>G		intron_variant	Intron 3 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000423517.6	c.3301-50407A>G		intron_variant	Intron 3 of 19	5		ENSP00000388393.2
PCLO	ENST00000461143.1	n.362-50407A>G		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72474 AN: 151814 Hom.: 19632 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.477 AC: 72481 AN: 151934 Hom.: 19643 Cov.: 31 AF XY: 0.472 AC XY: 35065 AN XY: 74246

African (AFR) AF: 0.260 AC: 10783 AN: 41448

American (AMR) AF: 0.348 AC: 5301 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1108 AN: 5164

South Asian (SAS) AF: 0.525 AC: 2533 AN: 4824

European-Finnish (FIN) AF: 0.602 AC: 6357 AN: 10552

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42517 AN: 67926

Other (OTH) AF: 0.474 AC: 998 AN: 2106

Alfa AF: 0.575 Hom.: 98094

Bravo AF: 0.446

Asia WGS AF: 0.344 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.75
PhyloP100		-1.8
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: rs28156; hg19: chr7-82646210;