7-83096302-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_033026.6(PCLO):​c.3300+37948C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00023 in 151,866 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00023 (0 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00023 (35/151866) while in subpopulation NFE AF = 0.000427 (29/67910). AF 95% confidence interval is 0.000305. There are 0 homozygotes in GnomAd4. There are 22 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

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+37948C>A		intron	N/A	NP_149015.2
	PCLO	NM_014510.3		c.3300+37948C>A		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+37948C>A		intron	N/A	ENSP00000334319.8
	PCLO	ENST00000423517.6	TSL:5	c.3300+37948C>A		intron	N/A	ENSP00000388393.2
	PCLO	ENST00000461143.1	TSL:2	n.361+37948C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000231 AC: 35 AN: 151748 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.000480

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

GnomAD4 genome AF: 0.000230 AC: 35 AN: 151866 Hom.: 0 Cov.: 31 AF XY: 0.000297 AC XY: 22 AN XY: 74198

African (AFR) AF: 0.0000241 AC: 1 AN: 41428

American (AMR) AF: 0.000197 AC: 3 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67910

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.0000926 Hom.: 612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
DANN	Benign	0.75
PhyloP100		-0.39

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;