chr12-41188585-C-T

Position:

• chr12-41188585-C-T

Variant summary

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

The NM_001164595.2(PDZRN4):​c.130C>T​(p.Pro44Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,391,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PDZRN4 NM_001164595.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16

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=0.3653595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZRN4	NM_001164595.2	c.130C>T	p.Pro44Ser	missense_variant	1/10	ENST00000402685.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZRN4	ENST00000402685.7	c.130C>T	p.Pro44Ser	missense_variant	1/10	2	NM_001164595.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1391596 Hom.: 0 Cov.: 32 AF XY: 0.00000291 AC XY: 2 AN XY: 687582

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

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

Jan 29, 2024

The c.130C>T (p.P44S) alteration is located in exon 1 (coding exon 1) of the PDZRN4 gene. This alteration results from a C to T substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a serine (S). 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	0.24
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.017
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.26	N
MutationTaster	Benign	0.93	D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.11
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.015	D
Vest4		0.47
MutPred		0.46		Gain of catalytic residue at S40 (P = 0);
MVP		0.59
MPC		1.9
ClinPred		0.89	D
GERP RS		2.5
Varity_R		0.21
gMVP		0.20

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: rs936685241; hg19: chr12-41582387;