1-61899649-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001350145.3(PATJ):c.3198G>A(p.Pro1066=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000466 in 1,605,576 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00078 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00043 (4 hom.)
• Consequence: PATJ NM_001350145.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.103

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 1-61899649-G-A is Benign according to our data. Variant chr1-61899649-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.103 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.3198G>A	p.Pro1066=	synonymous_variant	23/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.3198G>A	p.Pro1066=	synonymous_variant	23/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.000783 AC: 119 AN: 151958 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00887

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000906 AC: 224 AN: 247372 Hom.: 4 AF XY: 0.000865 AC XY: 116 AN XY: 134092

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00921

Gnomad SAS exome AF: 0.000231

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000248

Gnomad OTH exome AF: 0.00100

GnomAD4 exome AF: 0.000433 AC: 630 AN: 1453500 Hom.: 4 Cov.: 29 AF XY: 0.000415 AC XY: 300 AN XY: 723708

Gnomad4 AFR exome AF: 0.00140

Gnomad4 AMR exome AF: 0.0000464

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00463

Gnomad4 SAS exome AF: 0.000233

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000266

Gnomad4 OTH exome AF: 0.00138

GnomAD4 genome AF: 0.000783 AC: 119 AN: 152076 Hom.: 0 Cov.: 31 AF XY: 0.000740 AC XY: 55 AN XY: 74326

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00889

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000503 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.00866 AC: 30 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

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

Nov 01, 2022

PATJ: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
Cadd	Benign	7.5
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116844048; hg19: chr1-62365321; COSMIC: COSV100334612;