1-61775343-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001350145.3(PATJ):c.849+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,597,850 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (51 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (36 hom.)
• Consequence: PATJ NM_001350145.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.95

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 1-61775343-A-G is Benign according to our data. Variant chr1-61775343-A-G is described in ClinVar as [Benign]. Clinvar id is 775553.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0133 (2025/152302) while in subpopulation AFR AF= 0.0465 (1932/41560). AF 95% confidence interval is 0.0448. There are 51 homozygotes in gnomad4. There are 886 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.849+9A>G		intron_variant		ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.849+9A>G		intron_variant			NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2016 AN: 152184 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00370 AC: 867 AN: 234214 Hom.: 17 AF XY: 0.00253 AC XY: 320 AN XY: 126596

Gnomad AFR exome AF: 0.0486

Gnomad AMR exome AF: 0.00228

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000762

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.000878

GnomAD4 exome AF: 0.00136 AC: 1963 AN: 1445548 Hom.: 36 Cov.: 30 AF XY: 0.00116 AC XY: 834 AN XY: 718620

Gnomad4 AFR exome AF: 0.0480

Gnomad4 AMR exome AF: 0.00278

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000486

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000966

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.0133 AC: 2025 AN: 152302 Hom.: 51 Cov.: 32 AF XY: 0.0119 AC XY: 886 AN XY: 74474

Gnomad4 AFR AF: 0.0465

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00660 Hom.: 12

Bravo AF: 0.0155

Asia WGS AF: 0.00375 AC: 13 AN: 3478

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	17
Dann	Benign	0.64

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: rs79388226; hg19: chr1-62241015;