1-62052275-C-T

Position:

• chr1-62052275-C-T

Variant summary

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

The NM_001350145.3(PATJ):​c.4125+1217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,032 control chromosomes in the GnomAD database, including 722 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 0.091 (722 hom., cov: 31)
• Consequence: PATJ NM_001350145.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.647

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PATJ	NM_001350145.3	c.4125+1217C>T		intron_variant		ENST00000642238.2	NP_001337074.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PATJ	ENST00000642238.2	c.4125+1217C>T		intron_variant			NM_001350145.3	ENSP00000494277.1

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13826 AN: 151914 Hom.: 720 Cov.: 31

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.0695

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.0805

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0910 AC: 13835 AN: 152032 Hom.: 722 Cov.: 31 AF XY: 0.0905 AC XY: 6721 AN XY: 74304

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.0696

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.0927

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0917 Hom.: 373

Bravo AF: 0.0831

Asia WGS AF: 0.0730 AC: 253 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.7
DANN	Benign	0.59

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: rs991007; hg19: chr1-62517947; COSMIC: COSV56248380;