ENST00000377861.4:c.*10391_*10406dupATATATATATATATAT

Variant names:

• chr13-67214935-G-GATATATATATATATAT
• rs66460017
• ENST00000377861.4:c.*10391_*10406dupATATATATATATATAT

Variant summary

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

The ENST00000377861.4(PCDH9):​c.*10391_*10406dupATATATATATATATAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.033 (769 hom., cov: 0)
• Consequence: PCDH9 ENST00000377861.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• 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 nfe. GnomAd4 allele frequency = 0.0326 (2901/88954) while in subpopulation NFE AF = 0.04 (1691/42228). AF 95% confidence interval is 0.0385. There are 769 homozygotes in GnomAd4. There are 1233 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2901 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377861.4. 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+10454_3036+10469dupATATATATATATATAT		intron	N/A	NP_982354.1	X5D7N0
	PCDH9	NM_001318374.2		c.*10391_*10406dupATATATATATATATAT		3_prime_UTR	Exon 2 of 2	NP_001305303.1	Q5VT82
	PCDH9	NM_020403.5		c.3036+10454_3036+10469dupATATATATATATATAT		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.*10391_*10406dupATATATATATATATAT		3_prime_UTR	Exon 2 of 2	ENSP00000367092.3	Q5VT82
	PCDH9	ENST00000377865.7	TSL:1 MANE Select	c.3036+10454_3036+10469dupATATATATATATATAT		intron	N/A	ENSP00000367096.2	Q9HC56-1
	PCDH9	ENST00000544246.5	TSL:1	c.3036+10454_3036+10469dupATATATATATATATAT		intron	N/A	ENSP00000442186.2	Q9HC56-2

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 2899 AN: 88910 Hom.: 768 Cov.: 0

Gnomad AFR AF: 0.0278

Gnomad AMI AF: 0.00432

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0765

Gnomad EAS AF: 0.0293

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.00397

Gnomad MID AF: 0.0247

Gnomad NFE AF: 0.0400

Gnomad OTH AF: 0.0385

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0326 AC: 2901 AN: 88954 Hom.: 769 Cov.: 0 AF XY: 0.0289 AC XY: 1233 AN XY: 42724

African (AFR) AF: 0.0278 AC: 623 AN: 22410

American (AMR) AF: 0.0190 AC: 155 AN: 8140

Ashkenazi Jewish (ASJ) AF: 0.0765 AC: 189 AN: 2472

East Asian (EAS) AF: 0.0293 AC: 90 AN: 3072

South Asian (SAS) AF: 0.0256 AC: 79 AN: 3086

European-Finnish (FIN) AF: 0.00397 AC: 22 AN: 5546

Middle Eastern (MID) AF: 0.0197 AC: 3 AN: 152

European-Non Finnish (NFE) AF: 0.0400 AC: 1691 AN: 42228

Other (OTH) AF: 0.0399 AC: 46 AN: 1154

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs66460017; hg19: chr13-67789067;