12-41188636-C-G

Position:

• chr12-41188636-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001164595.2(PDZRN4):​c.181C>G​(p.Pro61Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PDZRN4 NM_001164595.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27913952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZRN4	NM_001164595.2	c.181C>G	p.Pro61Ala	missense_variant	1/10	ENST00000402685.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZRN4	ENST00000402685.7	c.181C>G	p.Pro61Ala	missense_variant	1/10	2	NM_001164595.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 15, 2023

The c.181C>G (p.P61A) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a C to G substitution at nucleotide position 181, causing the proline (P) at amino acid position 61 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.49	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.90	N
MutationTaster	Benign	0.92	N
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.45
MutPred		0.45		Gain of catalytic residue at P61 (P = 0.0019);
MVP		0.74
MPC		1.5
ClinPred		0.18	T
GERP RS		2.0
Varity_R		0.051
gMVP		0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-41582438;