rs2299754

Variant names:

• chr21-39889365-C-T
• rs2299754
• NM_006198.3:c.10-9111C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006198.3(PCP4):​c.10-9111C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,394 control chromosomes in the GnomAD database, including 1,348 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 0.13 (1348 hom., cov: 30)
• Consequence: PCP4 NM_006198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132
• Publications: 2 publications found

Genes affected

PCP4 (HGNC:8742): (Purkinje cell protein 4) Enables calcium ion binding activity and calmodulin binding activity. Involved in calmodulin dependent kinase signaling pathway and positive regulation of neuron differentiation. Located in cytosol and nucleus. Part of protein-containing complex. Biomarker of Huntington's disease and leiomyoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCP4	NM_006198.3	c.10-9111C>T		intron_variant	Intron 1 of 2	ENST00000328619.10	NP_006189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCP4	ENST00000328619.10	c.10-9111C>T		intron_variant	Intron 1 of 2	1	NM_006198.3	ENSP00000329403.5
PCP4	ENST00000462224.5	n.10-9111C>T		intron_variant	Intron 1 of 3	2		ENSP00000433172.1
PCP4	ENST00000468717.5	n.240+5733C>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18953 AN: 151274 Hom.: 1343 Cov.: 30

Gnomad AFR AF: 0.0643

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.0921

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.125 AC: 18963 AN: 151394 Hom.: 1348 Cov.: 30 AF XY: 0.127 AC XY: 9385 AN XY: 73872

African (AFR) AF: 0.0643 AC: 2656 AN: 41296

American (AMR) AF: 0.192 AC: 2899 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.0642 AC: 223 AN: 3472

East Asian (EAS) AF: 0.216 AC: 1109 AN: 5134

South Asian (SAS) AF: 0.0918 AC: 439 AN: 4784

European-Finnish (FIN) AF: 0.163 AC: 1686 AN: 10352

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9589 AN: 67910

Other (OTH) AF: 0.128 AC: 271 AN: 2112

Alfa AF: 0.135 Hom.: 2383

Bravo AF: 0.129

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.5
DANN	Benign	0.42
PhyloP100		-0.13
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: rs2299754; hg19: chr21-41261290;