Variant chr10-101008491-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001195263.2(PDZD7):c.3078C>T(p.Pro1026Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,526,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

PDZD7
NM_001195263.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.16

Variant links:

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]

PDZD7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 10-101008491-G-A is Benign according to our data. Variant chr10-101008491-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 929883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.16 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2 linkuse as main transcript	c.3078C>T	p.Pro1026Pro	synonymous_variant	17/17	ENST00000619208.6	NP_001182192.1	Q9H5P4-3
PDZD7	XM_011540177.4 linkuse as main transcript	c.3078C>T	p.Pro1026Pro	synonymous_variant	18/18		XP_011538479.1	Q9H5P4-3
PDZD7	XM_047425767.1 linkuse as main transcript	c.3078C>T	p.Pro1026Pro	synonymous_variant	17/17		XP_047281723.1
PDZD7	XM_011540178.4 linkuse as main transcript	c.3075C>T	p.Pro1025Pro	synonymous_variant	17/17		XP_011538480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PDZD7	ENST00000619208.6 linkuse as main transcript	c.3078C>T	p.Pro1026Pro	synonymous_variant	17/17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 linkuse as main transcript	n.*3025C>T		non_coding_transcript_exon_variant	13/13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 linkuse as main transcript	n.*3025C>T		3_prime_UTR_variant	13/13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00465

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000343

AC:

AN:

131064

Hom.:

AF XY:

0.000340

AC XY:

AN XY:

70570

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00368

Gnomad SAS exome

AF:

0.000142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000388

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000112

AC:

154

AN:

1374898

Hom.:

Cov.:

AF XY:

0.000112

AC XY:

AN XY:

677192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00281

Gnomad4 SAS exome

AF:

0.000218

Gnomad4 FIN exome

AF:

0.0000294

Gnomad4 NFE exome

AF:

0.0000251

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000178

AC:

AN:

152008

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00466

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.000325

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 03, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2021	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Pro1026Pro in exon 17 of PDZD7: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.06% (2/3440) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs534463809). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.42

DANN

Benign

0.57

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over