1-61914452-A-G

Position:

• chr1-61914452-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001350145.3(PATJ):​c.3493-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 450,278 control chromosomes in the GnomAD database, including 99,729 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (31577 hom., cov: 31)
  • Exomes 𝑓: 0.67 (68152 hom.)
• Consequence: PATJ NM_001350145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.3493-135A>G		intron_variant		ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.3493-135A>G		intron_variant			NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97475 AN: 151844 Hom.: 31550 Cov.: 31

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.764

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.619

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.671 AC: 200244 AN: 298318 Hom.: 68152 AF XY: 0.676 AC XY: 108210 AN XY: 159996

Gnomad4 AFR exome AF: 0.613

Gnomad4 AMR exome AF: 0.704

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.790

Gnomad4 SAS exome AF: 0.782

Gnomad4 FIN exome AF: 0.705

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.642 AC: 97555 AN: 151960 Hom.: 31577 Cov.: 31 AF XY: 0.649 AC XY: 48180 AN XY: 74274

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.694

Gnomad4 NFE AF: 0.619

Gnomad4 OTH AF: 0.632

Alfa AF: 0.627 Hom.: 28042

Bravo AF: 0.638

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.1
DANN	Benign	0.71

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: rs4915789; hg19: chr1-62380124;