7-83083832-C-T

Variant names:

• chr7-83083832-C-T
• rs10487657
• NM_033026.6:c.3300+50418G>A

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+50418G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,890 control chromosomes in the GnomAD database, including 18,308 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 0.49 (18308 hom., cov: 32)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.3300+50418G>A		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.3300+50418G>A		intron_variant	Intron 3 of 24	2	NM_033026.6	ENSP00000334319.8
PCLO	ENST00000423517.6	c.3300+50418G>A		intron_variant	Intron 3 of 19	5		ENSP00000388393.2
PCLO	ENST00000461143.1	n.361+50418G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74229 AN: 151772 Hom.: 18288 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.493

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

GnomAD4 genome AF: 0.489 AC: 74296 AN: 151890 Hom.: 18308 Cov.: 32 AF XY: 0.491 AC XY: 36396 AN XY: 74196

African (AFR) AF: 0.507 AC: 20989 AN: 41410

American (AMR) AF: 0.503 AC: 7669 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1801 AN: 3468

East Asian (EAS) AF: 0.276 AC: 1426 AN: 5164

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4824

European-Finnish (FIN) AF: 0.508 AC: 5359 AN: 10558

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33059 AN: 67904

Other (OTH) AF: 0.494 AC: 1041 AN: 2108

Alfa AF: 0.486 Hom.: 75876

Bravo AF: 0.487

Asia WGS AF: 0.401 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.33
DANN	Benign	0.54
PhyloP100		-0.79
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: rs10487657; hg19: chr7-82713148;