12-41552737-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164595.2(PDZRN4):​c.1285G>A​(p.Gly429Ser) variant causes a missense change. The variant allele was found at a frequency of 0.163 in 1,611,684 control chromosomes in the GnomAD database, including 22,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2585 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19906 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017770231).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164595.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZRN4	NM_001164595.2	MANE Select	c.1285G>A	p.Gly429Ser	missense	Exon 6 of 10	NP_001158067.1
	PDZRN4	NM_013377.4		c.511G>A	p.Gly171Ser	missense	Exon 4 of 8	NP_037509.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZRN4	ENST00000402685.7	TSL:2 MANE Select	c.1285G>A	p.Gly429Ser	missense	Exon 6 of 10	ENSP00000384197.2
	PDZRN4	ENST00000539469.6	TSL:1	c.511G>A	p.Gly171Ser	missense	Exon 4 of 8	ENSP00000439990.2
	PDZRN4	ENST00000548316.1	TSL:1	n.445G>A		non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27443 AN: 151850 Hom.: 2584 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.0978

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.175

GnomAD2 exomes AF: 0.158 AC: 39614 AN: 250912 AF XY: 0.161

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.0770

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.0942

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.161 AC: 234743 AN: 1459714 Hom.: 19906 Cov.: 32 AF XY: 0.162 AC XY: 117904 AN XY: 726268

African (AFR) AF: 0.241 AC: 8051 AN: 33416

American (AMR) AF: 0.0837 AC: 3742 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4586 AN: 26094

East Asian (EAS) AF: 0.107 AC: 4225 AN: 39646

South Asian (SAS) AF: 0.179 AC: 15410 AN: 86178

European-Finnish (FIN) AF: 0.189 AC: 10062 AN: 53342

Middle Eastern (MID) AF: 0.237 AC: 1366 AN: 5756

European-Non Finnish (NFE) AF: 0.160 AC: 177483 AN: 1110274

Other (OTH) AF: 0.163 AC: 9818 AN: 60310

GnomAD4 genome AF: 0.181 AC: 27452 AN: 151970 Hom.: 2585 Cov.: 32 AF XY: 0.179 AC XY: 13305 AN XY: 74258

African (AFR) AF: 0.241 AC: 9986 AN: 41416

American (AMR) AF: 0.121 AC: 1841 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 633 AN: 3466

East Asian (EAS) AF: 0.0974 AC: 503 AN: 5164

South Asian (SAS) AF: 0.172 AC: 828 AN: 4810

European-Finnish (FIN) AF: 0.189 AC: 1997 AN: 10562

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11146 AN: 67982

Other (OTH) AF: 0.173 AC: 364 AN: 2106

Alfa AF: 0.167 Hom.: 10165

Bravo AF: 0.176

TwinsUK AF: 0.152 AC: 562

ALSPAC AF: 0.157 AC: 605

ESP6500AA AF: 0.239 AC: 1055

ESP6500EA AF: 0.161 AC: 1387

ExAC AF: 0.165 AC: 20013

Asia WGS AF: 0.141 AC: 495 AN: 3478

EpiCase AF: 0.163

EpiControl AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.050	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	1.6	L
PhyloP100		6.7
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.29
Sift	Benign	0.10	T
Sift4G	Benign	0.083	T
Polyphen		1.0	D
Vest4		0.27
MPC		0.41
ClinPred		0.019	T
GERP RS		5.0
Varity_R		0.58
gMVP		0.68
Mutation Taster		=95/5	polymorphism (auto)

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; COSMIC: COSV54194883;