1-61861632-G-C

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.2404G>C(p.Asp802His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,471,416 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (39 hom., cov: 30)
  • Exomes 𝑓: 0.0010 (26 hom.)
• Consequence: PATJ NM_001350145.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

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 (MetaRNN=0.002489537).
• BP6: Variant 1-61861632-G-C is Benign according to our data. Variant chr1-61861632-G-C is described in ClinVar as [Benign]. Clinvar id is 775134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1754/152108) while in subpopulation AFR AF= 0.0403 (1670/41484). AF 95% confidence interval is 0.0386. There are 39 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 39 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.2404G>C	p.Asp802His	missense_variant	19/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.2404G>C	p.Asp802His	missense_variant	19/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1751 AN: 151990 Hom.: 39 Cov.: 30

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00291 AC: 534 AN: 183542 Hom.: 12 AF XY: 0.00215 AC XY: 219 AN XY: 101676

Gnomad AFR exome AF: 0.0409

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000497

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00153

GnomAD4 exome AF: 0.00103 AC: 1355 AN: 1319308 Hom.: 26 Cov.: 22 AF XY: 0.000950 AC XY: 625 AN XY: 658176

Gnomad4 AFR exome AF: 0.0391

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000869

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000894

Gnomad4 OTH exome AF: 0.00264

GnomAD4 genome AF: 0.0115 AC: 1754 AN: 152108 Hom.: 39 Cov.: 30 AF XY: 0.0110 AC XY: 821 AN XY: 74368

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.00380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.000736 Hom.: 1

Bravo AF: 0.0139

ESP6500AA AF: 0.0404 AC: 177

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00391 AC: 474

Asia WGS AF: 0.00173 AC: 6 AN: 3476

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

May 31, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.57
Cadd	Uncertain	23
Dann	Uncertain	0.99
Eigen	Benign	-0.0034
Eigen_PC	Benign	-0.070
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.84	T;T;T;T
MetaRNN	Benign	0.0025	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.32	T
Polyphen		0.76	.;.;P;.
Vest4		0.25, 0.18
MVP		0.56
MPC		0.48
ClinPred		0.039	T
GERP RS		2.4
Varity_R		0.055
gMVP		0.38

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: rs116544267; hg19: chr1-62327304;