13-67214935-GATATATATATATATATATATATATATATAT-GATATATATATATATATATATATATAT

Variant names:

• chr13-67214935-GATAT-G
• rs66460017
• ENST00000377861.4:c.*10403_*10406delATAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001318374.2(PCDH9):​c.*10403_*10406delATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (143 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: PCDH9 NM_001318374.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 0 publications found

Genes affected

PCDH9 (HGNC:8661): (protocadherin 9) This gene encodes a member of the protocadherin family, and cadherin superfamily, of transmembrane proteins containing cadherin domains. These proteins mediate cell adhesion in neural tissues in the presence of calcium. The encoded protein may be involved in signaling at neuronal synaptic junctions. Sharing a characteristic with other protocadherin genes, this gene has a notably large exon that encodes multiple cadherin domains and a transmembrane region. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0244 (2174/89090) while in subpopulation AFR AF = 0.049 (1100/22438). AF 95% confidence interval is 0.0466. There are 143 homozygotes in GnomAd4. There are 1103 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2174 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318374.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	NM_203487.3	MANE Select	c.3036+10466_3036+10469delATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10403_*10406delATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10466_3036+10469delATAT		intron	N/A	NP_065136.1	Q9HC56-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCDH9	ENST00000377861.4	TSL:1	c.*10403_*10406delATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10466_3036+10469delATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10466_3036+10469delATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0245 AC: 2178 AN: 89048 Hom.: 143 Cov.: 0

Gnomad AFR AF: 0.0489

Gnomad AMI AF: 0.00576

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.0320

Gnomad FIN AF: 0.0378

Gnomad MID AF: 0.0366

Gnomad NFE AF: 0.0103

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0244 AC: 2174 AN: 89090 Hom.: 143 Cov.: 0 AF XY: 0.0258 AC XY: 1103 AN XY: 42784

African (AFR) AF: 0.0490 AC: 1100 AN: 22438

American (AMR) AF: 0.0223 AC: 183 AN: 8202

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 25 AN: 2482

East Asian (EAS) AF: 0.0322 AC: 99 AN: 3070

South Asian (SAS) AF: 0.0310 AC: 96 AN: 3092

European-Finnish (FIN) AF: 0.0378 AC: 208 AN: 5500

Middle Eastern (MID) AF: 0.0195 AC: 3 AN: 154

European-Non Finnish (NFE) AF: 0.0103 AC: 434 AN: 42294

Other (OTH) AF: 0.0189 AC: 22 AN: 1164

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72
Mutation Taster		=100/0	polymorphism

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: rs66460017; hg19: chr13-67789067;