1-61864462-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001350145.3(PATJ):c.2664G>A(p.Leu888=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00985 in 1,613,954 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (6 hom., cov: 32)
  • Exomes 𝑓: 0.010 (99 hom.)
• Consequence: PATJ NM_001350145.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0800

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-61864462-G-A is Benign according to our data. Variant chr1-61864462-G-A is described in ClinVar as [Benign]. Clinvar id is 779063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.08 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.2664G>A	p.Leu888=	synonymous_variant	20/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.2664G>A	p.Leu888=	synonymous_variant	20/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.00794 AC: 1209 AN: 152192 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00224

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0120

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00777 AC: 1954 AN: 251418 Hom.: 20 AF XY: 0.00771 AC XY: 1047 AN XY: 135880

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00149

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00134

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0127

GnomAD4 exome AF: 0.0100 AC: 14684 AN: 1461644 Hom.: 99 Cov.: 33 AF XY: 0.00965 AC XY: 7018 AN XY: 727150

Gnomad4 AFR exome AF: 0.00146

Gnomad4 AMR exome AF: 0.00391

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00124

Gnomad4 FIN exome AF: 0.0208

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.00795

GnomAD4 genome AF: 0.00793 AC: 1208 AN: 152310 Hom.: 6 Cov.: 32 AF XY: 0.00779 AC XY: 580 AN XY: 74472

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0120

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00918 Hom.: 7

Bravo AF: 0.00622

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.0105

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 02, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	1.8
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs4915787; hg19: chr1-62330134;