chr3-73624174-T-C

Variant names:

• chr3-73624174-T-C
• rs773356609
• NM_015009.3:c.652A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015009.3(PDZRN3):​c.652A>G​(p.Lys218Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDZRN3 NM_015009.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.92
• Publications: 0 publications found

Genes affected

PDZRN3 (HGNC:17704): (PDZ domain containing ring finger 3) This gene encodes a member of the LNX (Ligand of Numb Protein-X) family of RING-type ubiquitin E3 ligases. This protein may function in vascular morphogenesis and the differentiation of adipocytes, osteoblasts and myoblasts. This protein may be targeted for degradation by the human papilloma virus E6 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

PDZRN3-AS1 (HGNC:40814): (PDZRN3 antisense RNA 1)

ENSG00000278934 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16136912).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015009.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZRN3	NM_015009.3	MANE Select	c.652A>G	p.Lys218Glu	missense	Exon 1 of 10	NP_055824.1	Q9UPQ7-1
	PDZRN3-AS1	NR_046681.1		n.398+209T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDZRN3	ENST00000263666.9	TSL:1 MANE Select	c.652A>G	p.Lys218Glu	missense	Exon 1 of 10	ENSP00000263666.4	Q9UPQ7-1
	PDZRN3	ENST00000308537.4	TSL:1	c.652A>G	p.Lys218Glu	missense	Exon 1 of 4	ENSP00000308831.4	Q9UPQ7-2
	PDZRN3-AS1	ENST00000478988.3	TSL:5	n.380+209T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 101012 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1352248 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 667014

African (AFR) AF: 0.00 AC: 0 AN: 27924

American (AMR) AF: 0.00 AC: 0 AN: 30936

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23766

East Asian (EAS) AF: 0.00 AC: 0 AN: 31494

South Asian (SAS) AF: 0.00 AC: 0 AN: 75844

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5044

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1064290

Other (OTH) AF: 0.00 AC: 0 AN: 56160

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152102 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74310

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000184 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		2.9
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.12
Sift	Benign	0.40	T
Sift4G	Benign	0.27	T
Polyphen		0.88	P
Vest4		0.17
MutPred		0.37		Loss of MoRF binding (P = 0.0019)
MVP		0.51
MPC		1.8
ClinPred		0.44	T
GERP RS		5.0
Varity_R		0.30
gMVP		0.52
Mutation Taster		=56/44	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: rs773356609; hg19: chr3-73673325;