1-62017914-C-T

Position:

• chr1-62017914-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001350145.3(PATJ):​c.3926C>T​(p.Thr1309Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000947 in 1,612,042 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0052 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00051 (9 hom.)
• Consequence: PATJ NM_001350145.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.50

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]

LOC107984965 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007816225).
• BP6: Variant 1-62017914-C-T is Benign according to our data. Variant chr1-62017914-C-T is described in ClinVar as [Benign]. Clinvar id is 787747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00516 (785/152156) while in subpopulation AFR AF= 0.0179 (744/41498). AF 95% confidence interval is 0.0169. There are 6 homozygotes in gnomad4. There are 368 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PATJ	NM_001350145.3	c.3926C>T	p.Thr1309Ile	missense_variant	29/44	ENST00000642238.2
LOC107984965	XR_001738097.2	n.84-11186G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PATJ	ENST00000642238.2	c.3926C>T	p.Thr1309Ile	missense_variant	29/44		NM_001350145.3	P1

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 783 AN: 152040 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00132 AC: 332 AN: 251202 Hom.: 3 AF XY: 0.000943 AC XY: 128 AN XY: 135758

Gnomad AFR exome AF: 0.0182

Gnomad AMR exome AF: 0.000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000508 AC: 741 AN: 1459886 Hom.: 9 Cov.: 28 AF XY: 0.000424 AC XY: 308 AN XY: 726334

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000811

Gnomad4 OTH exome AF: 0.000929

GnomAD4 genome AF: 0.00516 AC: 785 AN: 152156 Hom.: 6 Cov.: 32 AF XY: 0.00495 AC XY: 368 AN XY: 74392

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.000956 Hom.: 1

Bravo AF: 0.00598

ESP6500AA AF: 0.0161 AC: 71

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00155 AC: 188

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.066	.;T;.;T;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
MetaRNN	Benign	0.0078	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;.;.;.
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.4	.;N;.;.;D
REVEL	Benign	0.087
Sift	Uncertain	0.021	.;D;.;.;T
Sift4G	Uncertain	0.025	.;D;.;T;T
Polyphen		0.99, 0.92	.;D;.;.;P
Vest4		0.27, 0.41, 0.40
MVP		0.72
MPC		0.49
ClinPred		0.032	T
GERP RS		5.2
Varity_R		0.32
gMVP		0.33

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: rs75900825; hg19: chr1-62483586;