10-53866870-GAA-GAAAA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_033056.4(PCDH15):c.3502-14_3502-13insTT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000188 in 1,480,158 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000073 (0 hom., cov: 22)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: PCDH15 NM_033056.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.936

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 10-53866870-G-GAA is Benign according to our data. Variant chr10-53866870-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1164363.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1	c.3502-14_3502-13insTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000644397.2
PCDH15	NM_033056.4	c.3502-14_3502-13insTT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000320301.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11	c.3502-14_3502-13insTT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_033056.4
PCDH15	ENST00000644397.2	c.3502-14_3502-13insTT		splice_polypyrimidine_tract_variant, intron_variant			NM_001384140.1

Frequencies

GnomAD3 genomes AF: 0.0000734 AC: 11 AN: 149952 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000489

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000664

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000998

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000891

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000201 AC: 268 AN: 1330104 Hom.: 0 Cov.: 23 AF XY: 0.000180 AC XY: 120 AN XY: 667968

Gnomad4 AFR exome AF: 0.000443

Gnomad4 AMR exome AF: 0.0000712

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000795

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.000115

Gnomad4 NFE exome AF: 0.000189

Gnomad4 OTH exome AF: 0.000216

GnomAD4 genome AF: 0.0000733 AC: 11 AN: 150054 Hom.: 0 Cov.: 22 AF XY: 0.0000547 AC XY: 4 AN XY: 73118

Gnomad4 AFR AF: 0.0000488

Gnomad4 AMR AF: 0.0000663

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000998

Gnomad4 NFE AF: 0.0000891

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 20, 2024

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs5785023; hg19: chr10-55626630;