rs1056513

Positions:

• chr1-61914626-G-A
• chr1-61914626-G-C

Variant summary

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

The NM_001350145.3(PATJ):​c.3532G>A​(p.Gly1178Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,560,270 control chromosomes in the GnomAD database, including 301,583 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (21663 hom., cov: 31)
  • Exomes 𝑓: 0.62 (279920 hom.)
• Consequence: PATJ NM_001350145.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.402

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 (MetaRNN=7.179983E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.3532G>A	p.Gly1178Ser	missense_variant	26/44	ENST00000642238.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.3532G>A	p.Gly1178Ser	missense_variant	26/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74428 AN: 151624 Hom.: 21672 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.499

GnomAD3 exomes AF: 0.567 AC: 141134 AN: 248850 Hom.: 42256 AF XY: 0.578 AC XY: 77746 AN XY: 134540

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.502

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.564

Gnomad SAS exome AF: 0.562

Gnomad FIN exome AF: 0.614

Gnomad NFE exome AF: 0.647

Gnomad OTH exome AF: 0.584

GnomAD4 exome AF: 0.622 AC: 876073 AN: 1408532 Hom.: 279920 Cov.: 27 AF XY: 0.622 AC XY: 437600 AN XY: 703290

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.616

Gnomad4 NFE exome AF: 0.654

Gnomad4 OTH exome AF: 0.580

GnomAD4 genome AF: 0.490 AC: 74419 AN: 151738 Hom.: 21663 Cov.: 31 AF XY: 0.492 AC XY: 36466 AN XY: 74132

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.557

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.501

Alfa AF: 0.599 Hom.: 51358

Bravo AF: 0.469

TwinsUK AF: 0.660 AC: 2449

ALSPAC AF: 0.666 AC: 2565

ESP6500AA AF: 0.162 AC: 714

ESP6500EA AF: 0.651 AC: 5597

ExAC AF: 0.564 AC: 68453

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.73
DANN	Benign	0.17
DEOGEN2	Benign	0.0045	.;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	0.0000072	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.2	.;N
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.2	.;N
REVEL	Benign	0.0060
Sift	Benign	0.75	.;T
Sift4G	Benign	0.76	.;T
Polyphen		0.0	.;B
Vest4		0.0080
MPC		0.14
ClinPred		0.00030	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.15

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: rs1056513; hg19: chr1-62380298; COSMIC: COSV57155044; COSMIC: COSV57155044;