rs17020368

Positions:

• chr4-133158677-T-C

Variant summary

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

The NM_032961.3(PCDH10):​c.2797+3654T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0542 in 152,186 control chromosomes in the GnomAD database, including 582 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 0.054 (582 hom., cov: 33)
• Consequence: PCDH10 NM_032961.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH10	NM_032961.3	c.2797+3654T>C		intron_variant		ENST00000264360.7
PCDH10	XM_011532150.2	c.2797+3654T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH10	ENST00000264360.7	c.2797+3654T>C		intron_variant		1	NM_032961.3	P1
PCDH10	ENST00000511112.2	n.131+3654T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8211 AN: 152068 Hom.: 573 Cov.: 33

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0265

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00562

Gnomad OTH AF: 0.0484

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

GnomAD4 genome AF: 0.0542 AC: 8253 AN: 152186 Hom.: 582 Cov.: 33 AF XY: 0.0524 AC XY: 3895 AN XY: 74402

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.0261

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.0196

Gnomad4 SAS AF: 0.0265

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.00562

Gnomad4 OTH AF: 0.0569

Alfa AF: 0.0326 Hom.: 39

Bravo AF: 0.0595

Asia WGS AF: 0.0820 AC: 284 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.76

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: rs17020368; hg19: chr4-134079832;