10-27413327-GC-GCC

Variant names:

• chr10-27413327-G-GC
• rs75297921
• ENST00000642324.1:c.923dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000642324.1(PTCHD3):​c.923dupG​(p.Ser309GlnfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 1,613,714 control chromosomes in the GnomAD database, including 95,899 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.32 (8052 hom., cov: 0)
  • Exomes 𝑓: 0.34 (87847 hom.)
• Consequence: PTCHD3 ENST00000642324.1 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454
• Publications: 2 publications found

Genes affected

PTCHD3 (HGNC:24776): (patched domain containing 3 (gene/pseudogene)) Predicted to be located in sperm midpiece. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000301548 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 10-27413327-G-GC is Benign according to our data. Variant chr10-27413327-G-GC is described in ClinVar as Benign. ClinVar VariationId is 403352.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTCHD3	NM_001034842.5	c.923dupG	p.Ser309GlnfsTer26	frameshift_variant	Exon 1 of 4		NP_001030014.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTCHD3	ENST00000642324.1	c.923dupG	p.Ser309GlnfsTer26	frameshift_variant	Exon 1 of 4			ENSP00000495205.1

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48562 AN: 151816 Hom.: 8049 Cov.: 0

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.305 AC: 76766 AN: 251296 AF XY: 0.310

Gnomad AFR exome AF: 0.280

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.347

Gnomad EAS exome AF: 0.158

Gnomad FIN exome AF: 0.294

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.315

GnomAD4 exome AF: 0.341 AC: 497738 AN: 1461780 Hom.: 87847 Cov.: 61 AF XY: 0.340 AC XY: 246978 AN XY: 727194

African (AFR) AF: 0.278 AC: 9306 AN: 33478

American (AMR) AF: 0.249 AC: 11120 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8982 AN: 26136

East Asian (EAS) AF: 0.130 AC: 5153 AN: 39700

South Asian (SAS) AF: 0.298 AC: 25737 AN: 86254

European-Finnish (FIN) AF: 0.300 AC: 16032 AN: 53414

Middle Eastern (MID) AF: 0.324 AC: 1867 AN: 5768

European-Non Finnish (NFE) AF: 0.359 AC: 399224 AN: 1111920

Other (OTH) AF: 0.336 AC: 20317 AN: 60390

GnomAD4 genome AF: 0.320 AC: 48575 AN: 151934 Hom.: 8052 Cov.: 0 AF XY: 0.318 AC XY: 23602 AN XY: 74298

African (AFR) AF: 0.281 AC: 11645 AN: 41446

American (AMR) AF: 0.325 AC: 4963 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3470

East Asian (EAS) AF: 0.163 AC: 845 AN: 5186

South Asian (SAS) AF: 0.288 AC: 1384 AN: 4798

European-Finnish (FIN) AF: 0.294 AC: 3104 AN: 10570

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24198 AN: 67886

Other (OTH) AF: 0.344 AC: 727 AN: 2114

Alfa AF: 0.262 Hom.: 997

Bravo AF: 0.315

Asia WGS AF: 0.238 AC: 832 AN: 3478

EpiCase AF: 0.360

EpiControl AF: 0.363

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 584/2178=26.81%

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.45
Mutation Taster		=133/67	polymorphism (auto)

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: rs75297921; hg19: chr10-27702256; COSMIC: COSV71256259;