10-53806431-G-GTCTC

Position:

• chr10-53806431-G-GTCTC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001384140.1(PCDH15):​c.*147_*148insGAGA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 686,702 control chromosomes in the GnomAD database, including 370 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (260 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (110 hom.)
• Consequence: PCDH15 NM_001384140.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 10-53806431-G-GTCTC is Benign according to our data. Variant chr10-53806431-G-GTCTC is described in ClinVar as [Benign]. Clinvar id is 1260498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1	c.*147_*148insGAGA		3_prime_UTR_variant	38/38	ENST00000644397.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000644397.2	c.*147_*148insGAGA		3_prime_UTR_variant	38/38		NM_001384140.1

Frequencies

GnomAD3 genomes AF: 0.0326 AC: 4963 AN: 152052 Hom.: 260 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00721

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000912

Gnomad OTH AF: 0.0206

GnomAD4 exome AF: 0.00445 AC: 2379 AN: 534532 Hom.: 110 Cov.: 7 AF XY: 0.00400 AC XY: 1103 AN XY: 275598

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.00855

Gnomad4 ASJ exome AF: 0.00651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000734

Gnomad4 OTH exome AF: 0.00935

GnomAD4 genome AF: 0.0326 AC: 4964 AN: 152170 Hom.: 260 Cov.: 32 AF XY: 0.0312 AC XY: 2319 AN XY: 74406

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.0138

Gnomad4 ASJ AF: 0.00721

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.0206 Hom.: 19

Bravo AF: 0.0371

Asia WGS AF: 0.00694 AC: 25 AN: 3474

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

GeneDx

Dec 18, 2018

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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: rs149757971; hg19: chr10-55566191;