1-61856062-G-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001350145.3(PATJ):c.2145G>T(p.Val715=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,613,938 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: PATJ NM_001350145.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.57

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 1-61856062-G-T is Benign according to our data. Variant chr1-61856062-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2638857.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.57 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.2145G>T	p.Val715=	synonymous_variant	18/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.2145G>T	p.Val715=	synonymous_variant	18/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 114 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000713 AC: 179 AN: 251206 Hom.: 0 AF XY: 0.000641 AC XY: 87 AN XY: 135766

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00397

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.00108 AC: 1582 AN: 1461764 Hom.: 2 Cov.: 31 AF XY: 0.00104 AC XY: 754 AN XY: 727194

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00421

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.000749 AC: 114 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000565 AC XY: 42 AN XY: 74344

Gnomad4 AFR AF: 0.000193

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.00121 Hom.: 0

Bravo AF: 0.000733

EpiCase AF: 0.00131

EpiControl AF: 0.000889

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

Jul 01, 2022

PATJ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	7.4
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41289422; hg19: chr1-62321734;