Variant 10-101008507-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001195263.2(PDZD7):c.3062C>T(p.Thr1021Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

PDZD7
NM_001195263.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.515

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.076767296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZD7	NM_001195263.2 linkuse as main transcript	c.3062C>T	p.Thr1021Ile	missense_variant	17/17	ENST00000619208.6	NP_001182192.1	Q9H5P4-3
PDZD7	XM_011540177.4 linkuse as main transcript	c.3062C>T	p.Thr1021Ile	missense_variant	18/18		XP_011538479.1	Q9H5P4-3
PDZD7	XM_047425767.1 linkuse as main transcript	c.3062C>T	p.Thr1021Ile	missense_variant	17/17		XP_047281723.1
PDZD7	XM_011540178.4 linkuse as main transcript	c.3059C>T	p.Thr1020Ile	missense_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.3062C>T	p.Thr1021Ile	missense_variant	17/17	5	NM_001195263.2	ENSP00000480489.1	Q9H5P4-3
PDZD7	ENST00000474125.7 linkuse as main transcript	n.*3009C>T		non_coding_transcript_exon_variant	13/13	2		ENSP00000474447.1	S4R3J9
PDZD7	ENST00000474125.7 linkuse as main transcript	n.*3009C>T		3_prime_UTR_variant	13/13	2		ENSP00000474447.1	S4R3J9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000746

AC:

AN:

133966

Hom.:

AF XY:

0.0000138

AC XY:

AN XY:

72410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.24e-7

AC:

AN:

1380546

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.28e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Apr 26, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

4.9

DANN

Benign

0.71

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.38

.;T

MetaRNN

Benign

0.077

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

Sift4G

Uncertain

0.043

.;D

Vest4

0.11

MVP

0.043

ClinPred

0.044

GERP RS

0.36

Varity_R

0.039

gMVP

0.21

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