Variant chr1-61884254-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_001350145.3(PATJ):c.2977G>A(p.Val993Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PATJ
NM_001350145.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00500

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:

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=0.068906516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3 linkuse as main transcript	c.2977G>A	p.Val993Ile	missense_variant	22/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2 linkuse as main transcript	c.2977G>A	p.Val993Ile	missense_variant	22/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1453648

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723336

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:

0.00

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 specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.2977G>A (p.V993I) alteration is located in exon 22 (coding exon 21) of the PATJ gene. This alteration results from a G to A substitution at nucleotide position 2977, causing the valine (V) at amino acid position 993 to be replaced by an isoleucine (I). 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

Benign

0.072

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.3

DANN

Benign

0.81

DEOGEN2

Benign

0.0058

.;.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.57

T;T;T;T

M_CAP

Benign

0.0024

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

.;.;M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

0.12

.;N;N;.

REVEL

Benign

0.029

Sift

Benign

0.19

.;T;T;.

Sift4G

Benign

0.93

.;T;T;T

Polyphen

0.029

.;.;B;.

Vest4

0.088, 0.077

MutPred

0.32

Loss of disorder (P = 0.2671);Loss of disorder (P = 0.2671);Loss of disorder (P = 0.2671);Loss of disorder (P = 0.2671);

MVP

0.38

MPC

0.12

ClinPred

0.066

GERP RS

-0.60

Varity_R

0.017

gMVP

0.075

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over