rs2299753

Variant names:

• chr21-39888438-T-C
• rs2299753
• NM_006198.3:c.10-10038T>C

Variant summary

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

The NM_006198.3(PCP4):​c.10-10038T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,084 control chromosomes in the GnomAD database, including 9,253 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 0.32 (9253 hom., cov: 32)
• Consequence: PCP4 NM_006198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006198.3. 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
	PCP4	NM_006198.3	MANE Select	c.10-10038T>C		intron	N/A	NP_006189.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCP4	ENST00000328619.10	TSL:1 MANE Select	c.10-10038T>C		intron	N/A	ENSP00000329403.5
	PCP4	ENST00000462224.5	TSL:2	n.10-10038T>C		intron	N/A	ENSP00000433172.1
	PCP4	ENST00000468717.5	TSL:2	n.240+4806T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48125 AN: 151966 Hom.: 9223 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.317 AC: 48190 AN: 152084 Hom.: 9253 Cov.: 32 AF XY: 0.310 AC XY: 23041 AN XY: 74342

African (AFR) AF: 0.538 AC: 22319 AN: 41482

American (AMR) AF: 0.201 AC: 3079 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3464

East Asian (EAS) AF: 0.206 AC: 1067 AN: 5172

South Asian (SAS) AF: 0.278 AC: 1335 AN: 4810

European-Finnish (FIN) AF: 0.226 AC: 2395 AN: 10578

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16401 AN: 67978

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.280 Hom.: 1062

Bravo AF: 0.322

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0090
DANN	Benign	0.49
PhyloP100		-2.3
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: rs2299753; hg19: chr21-41260363;