chr1-61787911-C-A

Variant names:

• chr1-61787911-C-A
• rs142273680
• NM_001350145.3:c.1007C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001350145.3(PATJ):​c.1007C>A​(p.Pro336His) variant causes a missense change. The variant allele was found at a frequency of 0.0031 in 1,613,994 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (17 hom.)
• Consequence: PATJ NM_001350145.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.70
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010322511).
• BP6: Variant 1-61787911-C-A is Benign according to our data. Variant chr1-61787911-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3024715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 17 gene

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.1007C>A	p.Pro336His	missense	Exon 8 of 44	NP_001337074.2	A0A2R8Y549
	PATJ	NM_176877.5		c.1007C>A	p.Pro336His	missense	Exon 8 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.1007C>A	p.Pro336His	missense	Exon 8 of 44	ENSP00000494277.1	A0A2R8Y549
	PATJ	ENST00000459752.5	TSL:1	n.1121C>A		non_coding_transcript_exon	Exon 8 of 34
	PATJ	ENST00000484562.5	TSL:1	n.1121C>A		non_coding_transcript_exon	Exon 8 of 35

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 388 AN: 152122 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00381

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00281 AC: 706 AN: 251294 AF XY: 0.00268

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00359

Gnomad OTH exome AF: 0.00506

GnomAD4 exome AF: 0.00316 AC: 4616 AN: 1461754 Hom.: 17 Cov.: 32 AF XY: 0.00310 AC XY: 2255 AN XY: 727184

African (AFR) AF: 0.000747 AC: 25 AN: 33480

American (AMR) AF: 0.00262 AC: 117 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0134 AC: 349 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000475 AC: 41 AN: 86246

European-Finnish (FIN) AF: 0.000431 AC: 23 AN: 53412

Middle Eastern (MID) AF: 0.00123 AC: 7 AN: 5680

European-Non Finnish (NFE) AF: 0.00344 AC: 3823 AN: 1111994

Other (OTH) AF: 0.00383 AC: 231 AN: 60390

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152240 Hom.: 1 Cov.: 33 AF XY: 0.00227 AC XY: 169 AN XY: 74436

African (AFR) AF: 0.000698 AC: 29 AN: 41540

American (AMR) AF: 0.00262 AC: 40 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00381 AC: 259 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00357 Hom.: 7

Bravo AF: 0.00257

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00442 AC: 38

ExAC AF: 0.00278 AC: 338

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00404

EpiControl AF: 0.00433

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		4.7
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.61
MVP		0.74
MPC		0.69
ClinPred		0.025	T
GERP RS		5.1
Varity_R		0.50
gMVP		0.50
Mutation Taster		=90/10	polymorphism

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: rs142273680; hg19: chr1-62253583; COSMIC: COSV57162383;