chr4-133170579-G-A

Position:

• chr4-133170579-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032961.3(PCDH10):​c.3103+7297G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 152,190 control chromosomes in the GnomAD database, including 718 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 0.060 (718 hom., cov: 32)
• Consequence: PCDH10 NM_032961.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

Genes affected

PCDH10 (HGNC:13404): (protocadherin 10) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. This family member contains 6 extracellular cadherin domains, a transmembrane domain and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein is a cadherin-related neuronal receptor thought to function in the establishment of specific cell-cell connections in the brain. This gene plays a role in inhibiting cancer cell motility and cell migration. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2015]

PCDH10 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH10	NM_032961.3	c.3103+7297G>A		intron_variant		ENST00000264360.7	NP_116586.1
PCDH10	XM_011532150.2	c.3103+7297G>A		intron_variant			XP_011530452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH10	ENST00000264360.7	c.3103+7297G>A		intron_variant		1	NM_032961.3	ENSP00000264360.4
PCDH10	ENST00000511112.2	n.437+7297G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0594 AC: 9036 AN: 152072 Hom.: 709 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00565

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0596 AC: 9077 AN: 152190 Hom.: 718 Cov.: 32 AF XY: 0.0576 AC XY: 4283 AN XY: 74418

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0281

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.0193

Gnomad4 SAS AF: 0.0261

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.00565

Gnomad4 OTH AF: 0.0616

Alfa AF: 0.0151 Hom.: 114

Bravo AF: 0.0660

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.50
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518630; hg19: chr4-134091734;