1-61787911-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001350145.3(PATJ):c.1007C>A(p.Pro336His) variant causes a missense change. The variant allele was found at a frequency of 0.0031 in 1,613,994 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (17 hom.)
• Consequence: PATJ NM_001350145.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.70

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010322511).
• BP6: Variant 1-61787911-C-A is Benign according to our data. Variant chr1-61787911-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3024715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.1007C>A	p.Pro336His	missense_variant	8/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.1007C>A	p.Pro336His	missense_variant	8/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 152122 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00281 AC: 706 AN: 251294 Hom.: 5 AF XY: 0.00268 AC XY: 364 AN XY: 135802

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00359

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00316 AC: 4616 AN: 1461754 Hom.: 17 Cov.: 32 AF XY: 0.00310 AC XY: 2255 AN XY: 727184

Gnomad4 AFR exome AF: 0.000747

Gnomad4 AMR exome AF: 0.00262

Gnomad4 ASJ exome AF: 0.0134

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000475

Gnomad4 FIN exome AF: 0.000431

Gnomad4 NFE exome AF: 0.00344

Gnomad4 OTH exome AF: 0.00383

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152240 Hom.: 1 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74436

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00381

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00357 Hom.: 5

Bravo AF: 0.00257

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00278 AC: 338

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00404

EpiControl AF: 0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

PATJ: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
Cadd	Uncertain	24
Dann	Uncertain	1.0
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.010	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.45	T
Polyphen		1.0	.;.;D;.
Vest4		0.61, 0.56
MVP		0.74
MPC		0.69
ClinPred		0.025	T
GERP RS		5.1
Varity_R		0.50
gMVP		0.50

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

Other links and lift over

dbSNP: rs142273680; hg19: chr1-62253583; COSMIC: COSV57162383;