chr1-61914626-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350145.3(PATJ):​c.3532G>C​(p.Gly1178Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000211 in 1,423,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.056616426).

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>C	p.Gly1178Arg	missense	Exon 26 of 44	NP_001337074.2	A0A2R8Y549
	PATJ	NM_176877.5		c.3532G>C	p.Gly1178Arg	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>C	p.Gly1178Arg	missense	Exon 26 of 44	ENSP00000494277.1	A0A2R8Y549
	PATJ	ENST00000459752.5	TSL:1	n.3646G>C		non_coding_transcript_exon	Exon 26 of 34
	PATJ	ENST00000484562.5	TSL:1	n.3646G>C		non_coding_transcript_exon	Exon 26 of 35

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000804 AC: 2 AN: 248850 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1423256 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 710074

African (AFR) AF: 0.00 AC: 0 AN: 32742

American (AMR) AF: 0.00 AC: 0 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39386

South Asian (SAS) AF: 0.00 AC: 0 AN: 85286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52888

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5702

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078246

Other (OTH) AF: 0.00 AC: 0 AN: 58964

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 102612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	3.2
DANN	Benign	0.31
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.34	N
PhyloP100		0.40
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.32	N
REVEL	Benign	0.0080
Sift	Benign	0.52	T
Sift4G	Benign	0.53	T
Polyphen		0.0	B
Vest4		0.067
MutPred		0.34		Gain of MoRF binding (P = 0.0089)
MVP		0.35
MPC		0.17
ClinPred		0.026	T
GERP RS		2.3
PromoterAI		0.057	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.026
gMVP		0.21
Mutation Taster		=98/2	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: rs1056513; hg19: chr1-62380298;