12-41552737-G-T

Position:

• chr12-41552737-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G429S) has been classified as Likely benign.

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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/exons	MANE	UniProt
PDZRN4	NM_001164595.2	c.1285G>T	p.Gly429Cys	missense_variant	6/10	ENST00000402685.7
PDZRN4	NM_013377.4	c.511G>T	p.Gly171Cys	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZRN4	ENST00000402685.7	c.1285G>T	p.Gly429Cys	missense_variant	6/10	2	NM_001164595.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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;.;.;.
MutationTaster	Benign	5.2e-7	P;P;P
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
Polyphen		1.0	D;.;D;D
Vest4		0.73
MutPred		0.63		Gain of catalytic residue at E434 (P = 0.0054);.;.;.;
MVP		0.87
MPC		0.58
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.74
gMVP		0.72

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: rs285584; hg19: chr12-41946539;