rs1056513

Variant names:

• chr1-61914626-G-A
• rs1056513
• NM_001350145.3:c.3532G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350145.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATJ	NM_001350145.3	MANE Select	c.3532G>A	p.Gly1178Ser	missense	Exon 26 of 44	NP_001337074.2	A0A2R8Y549
	PATJ	NM_176877.5		c.3532G>A	p.Gly1178Ser	missense	Exon 26 of 43	NP_795352.3	Q8NI35-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PATJ	ENST00000642238.2	MANE Select	c.3532G>A	p.Gly1178Ser	missense	Exon 26 of 44	ENSP00000494277.1	A0A2R8Y549
	PATJ	ENST00000459752.5	TSL:1	n.3646G>A		non_coding_transcript_exon	Exon 26 of 34
	PATJ	ENST00000484562.5	TSL:1	n.3646G>A		non_coding_transcript_exon	Exon 26 of 35

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

GnomAD2 exomes AF: 0.567 AC: 141134 AN: 248850 AF XY: 0.578

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 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

African (AFR) AF: 0.132 AC: 4303 AN: 32618

American (AMR) AF: 0.504 AC: 22112 AN: 43908

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 12521 AN: 25650

East Asian (EAS) AF: 0.583 AC: 22900 AN: 39250

South Asian (SAS) AF: 0.563 AC: 47617 AN: 84640

European-Finnish (FIN) AF: 0.616 AC: 32480 AN: 52728

Middle Eastern (MID) AF: 0.566 AC: 3208 AN: 5670

European-Non Finnish (NFE) AF: 0.654 AC: 697097 AN: 1065688

Other (OTH) AF: 0.580 AC: 33835 AN: 58380

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

African (AFR) AF: 0.156 AC: 6420 AN: 41272

American (AMR) AF: 0.522 AC: 7966 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1708 AN: 3468

East Asian (EAS) AF: 0.586 AC: 3015 AN: 5144

South Asian (SAS) AF: 0.557 AC: 2677 AN: 4808

European-Finnish (FIN) AF: 0.618 AC: 6490 AN: 10510

Middle Eastern (MID) AF: 0.493 AC: 143 AN: 290

European-Non Finnish (NFE) AF: 0.652 AC: 44289 AN: 67974

Other (OTH) AF: 0.501 AC: 1054 AN: 2104

Alfa AF: 0.592 Hom.: 102612

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 v4.9

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
MetaRNN	Benign	0.0000072	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.2	N
PhyloP100		0.40
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
PromoterAI		-0.0081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.022
gMVP		0.15
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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