rs144469613

chr10-101019138-G-Achr10-101019138-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001195263.2(PDZD7):c.1008C>T(p.Pro336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00823 in 1,545,728 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0070 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0084 (57 hom.)
• Consequence: PDZD7 NM_001195263.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.24

Genes affected

PDZD7 (HGNC:26257): (PDZ domain containing 7) This gene encodes a ciliary protein homologous to proteins which are mutated in Usher syndrome patients, and mutations and translocations involving this gene have been associated with two types of Usher syndrome. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 10-101019138-G-A is Benign according to our data. Variant chr10-101019138-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00696 (1061/152388) while in subpopulation NFE AF= 0.00961 (654/68036). AF 95% confidence interval is 0.009. There are 4 homozygotes in gnomad4. There are 534 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZD7	NM_001195263.2	c.1008C>T	p.Pro336=	synonymous_variant	8/17	ENST00000619208.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZD7	ENST00000619208.6	c.1008C>T	p.Pro336=	synonymous_variant	8/17	5	NM_001195263.2	P1

Frequencies

GnomAD3 genomes AF: 0.00697 AC: 1061 AN: 152270 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00837

Gnomad ASJ AF: 0.00864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.0123

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00961

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00629 AC: 926 AN: 147152 Hom.: 5 AF XY: 0.00629 AC XY: 505 AN XY: 80332

Gnomad AFR exome AF: 0.00128

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.00651

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00228

Gnomad FIN exome AF: 0.00867

Gnomad NFE exome AF: 0.00992

Gnomad OTH exome AF: 0.00769

GnomAD4 exome AF: 0.00837 AC: 11658 AN: 1393340 Hom.: 57 Cov.: 33 AF XY: 0.00821 AC XY: 5654 AN XY: 688628

Gnomad4 AFR exome AF: 0.00130

Gnomad4 AMR exome AF: 0.00497

Gnomad4 ASJ exome AF: 0.00727

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00267

Gnomad4 FIN exome AF: 0.00752

Gnomad4 NFE exome AF: 0.00956

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00696 AC: 1061 AN: 152388 Hom.: 4 Cov.: 32 AF XY: 0.00717 AC XY: 534 AN XY: 74520

Gnomad4 AFR AF: 0.00195

Gnomad4 AMR AF: 0.00836

Gnomad4 ASJ AF: 0.00864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.0123

Gnomad4 NFE AF: 0.00961

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.00470 Hom.: 0

Bravo AF: 0.00628

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 06, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 18, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	PDZD7: BP4, BP7, BS2 -

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 09, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Pro336Pro in Exon 08 of PDZD7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 0.5% (35/6694) of Eur opean American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs144469613). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	14
Dann	Benign	0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs144469613; hg19: chr10-102778895;