Variant chr1-62017888-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001350145.3(PATJ):c.3900C>G(p.His1300Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000695 in 1,611,754 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

PATJ
NM_001350145.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.379

Variant links:

Genes affected

PATJ (HGNC:28881): (PATJ crumbs cell polarity complex component) This gene encodes a protein with multiple PDZ domains. PDZ domains mediate protein-protein interactions, and proteins with multiple PDZ domains often organize multimeric complexes at the plasma membrane. This protein localizes to tight junctions and to the apical membrane of epithelial cells. A similar protein in Drosophila is a scaffolding protein which tethers several members of a multimeric signaling complex in photoreceptors. [provided by RefSeq, Jul 2008]

PATJ links:

PATJ (HGNC:):

PATJ links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3754562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PATJ	NM_001350145.3 linkuse as main transcript	c.3900C>G	p.His1300Gln	missense_variant	29/44	ENST00000642238.2	NP_001337074.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PATJ	ENST00000642238.2 linkuse as main transcript	c.3900C>G	p.His1300Gln	missense_variant	29/44		NM_001350145.3	ENSP00000494277.1		A0A2R8Y549

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000717

AC:

AN:

251194

Hom.:

AF XY:

0.0000958

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.000150

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000685

AC:

100

AN:

1459588

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

726228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000856

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000324

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000123

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.3900C>G (p.H1300Q) alteration is located in exon 29 (coding exon 28) of the PATJ gene. This alteration results from a C to G substitution at nucleotide position 3900, causing the histidine (H) at amino acid position 1300 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.048

.;T;.;T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.85

LIST_S2

Pathogenic

0.99

D;D;D;D;D

M_CAP

Benign

0.038

MetaRNN

Benign

0.38

T;T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.2

.;M;.;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-6.5

.;D;.;.;D

REVEL

Uncertain

0.38

Sift

Benign

0.047

.;D;.;.;D

Sift4G

Uncertain

0.0030

.;D;.;D;D

Polyphen

1.0, 0.99

.;D;.;.;D

Vest4

0.79, 0.87, 0.82

MutPred

0.66

Loss of methylation at R1298 (P = 0.0838);Loss of methylation at R1298 (P = 0.0838);.;.;.;

MVP

0.69

MPC

0.59

ClinPred

0.61

GERP RS

3.2

Varity_R

0.71

gMVP

0.78

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

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