rs9316943

Positions:

• chr13-57724277-A-G
• chr13-57724277-A-T

Variant summary

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

The NM_001040429.3(PCDH17):​c.2798-335A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,000 control chromosomes in the GnomAD database, including 5,974 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 0.27 (5974 hom., cov: 32)
• Consequence: PCDH17 NM_001040429.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

Genes affected

PCDH17 (HGNC:14267): (protocadherin 17) This gene belongs to the protocadherin gene family, a subfamily of the cadherin superfamily. The encoded protein contains six extracellular cadherin domains, a transmembrane domain, and a cytoplasmic tail differing from those of the classical cadherins. The encoded protein may play a role in the establishment and function of specific cell-cell connections in the brain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH17	NM_001040429.3	c.2798-335A>G		intron_variant		ENST00000377918.8	NP_001035519.1
PCDH17	XM_005266357.3	c.2798-335A>G		intron_variant			XP_005266414.1
PCDH17	XM_047430276.1	c.2795-335A>G		intron_variant			XP_047286232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH17	ENST00000377918.8	c.2798-335A>G		intron_variant		1	NM_001040429.3	ENSP00000367151	P1
PCDH17	ENST00000484979.5	c.*136-335A>G		intron_variant, NMD_transcript_variant		1		ENSP00000432899
PCDH17	ENST00000612954.4	c.959-335A>G		intron_variant		5		ENSP00000481329
PCDH17	ENST00000615375.1	c.416-335A>G		intron_variant		4		ENSP00000483215

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41530 AN: 151882 Hom.: 5963 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.277

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.273 AC: 41565 AN: 152000 Hom.: 5974 Cov.: 32 AF XY: 0.278 AC XY: 20613 AN XY: 74266

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.237

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.277

Gnomad4 OTH AF: 0.275

Alfa AF: 0.267 Hom.: 3119

Bravo AF: 0.267

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.65

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: rs9316943; hg19: chr13-58298411;