12-41552737-G-T

Variant names:

• chr12-41552737-G-T
• rs285584
• NM_001164595.2:c.1285G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001164595.2(PDZRN4):​c.1285G>T​(p.Gly429Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDZRN4 NM_001164595.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.72
• Publications: 23 publications found

Genes affected

PDZRN4 (HGNC:30552): (PDZ domain containing ring finger 4) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000301531 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDZRN4	NM_001164595.2	c.1285G>T	p.Gly429Cys	missense_variant	Exon 6 of 10	ENST00000402685.7	NP_001158067.1
PDZRN4	NM_013377.4	c.511G>T	p.Gly171Cys	missense_variant	Exon 4 of 8		NP_037509.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDZRN4	ENST00000402685.7	c.1285G>T	p.Gly429Cys	missense_variant	Exon 6 of 10	2	NM_001164595.2	ENSP00000384197.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 10165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.;.;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.98	D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.88	D;D;D;D
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.4	M;.;.;.
PhyloP100		6.7
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.8	D;.;D;D
REVEL	Uncertain	0.49
Sift	Benign	0.031	D;.;D;T
Sift4G	Uncertain	0.0070	D;.;D;D
Vest4		0.73
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.74
gMVP		0.72
Mutation Taster		=82/18	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: rs285584; hg19: chr12-41946539;