chr7-82759398-T-G

Variant names:

• chr7-82759398-T-G
• rs13438494
• NM_033026.6:c.15289-683A>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.15289-683A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,560 control chromosomes in the GnomAD database, including 29,375 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 0.61 (29375 hom., cov: 31)
• Consequence: PCLO NM_033026.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 13 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCLO	NM_033026.6	c.15289-683A>C		intron_variant	Intron 24 of 24	ENST00000333891.14	NP_149015.2
PCLO	XM_047420210.1	c.15472-683A>C		intron_variant	Intron 25 of 25		XP_047276166.1
PCLO	XM_047420211.1	c.14998-683A>C		intron_variant	Intron 25 of 25		XP_047276167.1
PCLO	XM_017012006.3	c.8377-683A>C		intron_variant	Intron 23 of 23		XP_016867495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCLO	ENST00000333891.14	c.15289-683A>C		intron_variant	Intron 24 of 24	2	NM_033026.6	ENSP00000334319.8

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92361 AN: 151442 Hom.: 29309 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.610 AC: 92494 AN: 151560 Hom.: 29375 Cov.: 31 AF XY: 0.609 AC XY: 45134 AN XY: 74076

African (AFR) AF: 0.762 AC: 31524 AN: 41394

American (AMR) AF: 0.575 AC: 8741 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1727 AN: 3458

East Asian (EAS) AF: 0.850 AC: 4365 AN: 5136

South Asian (SAS) AF: 0.627 AC: 3022 AN: 4820

European-Finnish (FIN) AF: 0.513 AC: 5409 AN: 10536

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35770 AN: 67706

Other (OTH) AF: 0.584 AC: 1229 AN: 2106

Alfa AF: 0.568 Hom.: 40575

Bravo AF: 0.624

Asia WGS AF: 0.740 AC: 2570 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.77
PhyloP100		-0.12
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: rs13438494; hg19: chr7-82388714;