Variant 1-61914626-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001350145.3(PATJ):c.3532G>A(p.Gly1178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,560,270 control chromosomes in the GnomAD database, including 301,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 21663 hom., cov: 31)

Exomes 𝑓: 0.62 ( 279920 hom. )

Consequence

PATJ
NM_001350145.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.402

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.179983E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3 linkuse as main transcript	c.3532G>A	p.Gly1178Ser	missense_variant	26/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2 linkuse as main transcript	c.3532G>A	p.Gly1178Ser	missense_variant	26/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74428

AN:

151624

Hom.:

21672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.586

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.618

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.499

GnomAD3 exomes

AF:

0.567

AC:

141134

AN:

248850

Hom.:

42256

AF XY:

0.578

AC XY:

77746

AN XY:

134540

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.502

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.564

Gnomad SAS exome

AF:

0.562

Gnomad FIN exome

AF:

0.614

Gnomad NFE exome

AF:

0.647

Gnomad OTH exome

AF:

0.584

GnomAD4 exome

AF:

0.622

AC:

876073

AN:

1408532

Hom.:

279920

Cov.:

AF XY:

0.622

AC XY:

437600

AN XY:

703290

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.504

Gnomad4 ASJ exome

AF:

0.488

Gnomad4 EAS exome

AF:

0.583

Gnomad4 SAS exome

AF:

0.563

Gnomad4 FIN exome

AF:

0.616

Gnomad4 NFE exome

AF:

0.654

Gnomad4 OTH exome

AF:

0.580

GnomAD4 genome

AF:

0.490

AC:

74419

AN:

151738

Hom.:

21663

Cov.:

AF XY:

0.492

AC XY:

36466

AN XY:

74132

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.522

Gnomad4 ASJ

AF:

0.493

Gnomad4 EAS

AF:

0.586

Gnomad4 SAS

AF:

0.557

Gnomad4 FIN

AF:

0.618

Gnomad4 NFE

AF:

0.652

Gnomad4 OTH

AF:

0.501

Alfa

AF:

0.599

Hom.:

51358

Bravo

AF:

0.469

TwinsUK

AF:

0.660

AC:

2449

ALSPAC

AF:

0.666

AC:

2565

ESP6500AA

AF:

0.162

AC:

714

ESP6500EA

AF:

0.651

AC:

5597

ExAC

AF:

0.564

AC:

68453

Asia WGS

AF:

0.548

AC:

1907

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.73

DANN

Benign

0.17

DEOGEN2

Benign

0.0045

.;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.14

T;T

MetaRNN

Benign

0.0000072

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.2

.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

1.2

.;N

REVEL

Benign

0.0060

Sift

Benign

0.75

.;T

Sift4G

Benign

0.76

.;T

Polyphen

0.0

.;B

Vest4

0.0080

MPC

0.14

ClinPred

0.00030

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.15

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over