7-82949749-AGC-GGT

Variant names:

• chr7-82949749-AGC-GGT
• NM_033026.6:c.10837_10839delGCTinsACC
• PCLO p.Ala3613Thr

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_033026.6(PCLO):​c.10837_10839delGCTinsACC​(p.Ala3613Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3613S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PCLO NM_033026.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.23
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	NM_033026.6	MANE Select	c.10837_10839delGCTinsACC	p.Ala3613Thr	missense	N/A	NP_149015.2	Q9Y6V0-5
	PCLO	NM_014510.3		c.10837_10839delGCTinsACC	p.Ala3613Thr	missense	N/A	NP_055325.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCLO	ENST00000333891.14	TSL:2 MANE Select	c.10837_10839delGCTinsACC	p.Ala3613Thr	missense	N/A	ENSP00000334319.8	Q9Y6V0-5
	PCLO	ENST00000437081.2	TSL:1	c.997_999delGCTinsACC	p.Ala333Thr	missense	N/A	ENSP00000393760.2
	PCLO	ENST00000423517.6	TSL:5	c.10837_10839delGCTinsACC	p.Ala3613Thr	missense	N/A	ENSP00000388393.2	Q9Y6V0-6

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-82579065;