NM_002851.3:c.504A>C

Variant names:

• chr7-121976220-A-C
• rs1257076255
• NM_002851.3:c.504A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002851.3(PTPRZ1):​c.504A>C​(p.Glu168Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,609,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPRZ1 NM_002851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783
• Publications: 1 publications found

Genes affected

PTPRZ1 (HGNC:9685): (protein tyrosine phosphatase receptor type Z1) This gene encodes a member of the receptor protein tyrosine phosphatase family. Expression of this gene is restricted to the central nervous system (CNS), and it may be involved in the regulation of specific developmental processes in the CNS. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3168928).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002851.3. 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
	PTPRZ1	NM_002851.3	MANE Select	c.504A>C	p.Glu168Asp	missense	Exon 5 of 30	NP_002842.2	P23471-1
	PTPRZ1	NM_001369395.1		c.504A>C	p.Glu168Asp	missense	Exon 5 of 29	NP_001356324.1	P23471-2
	PTPRZ1	NM_001369396.1		c.462A>C	p.Glu154Asp	missense	Exon 6 of 31	NP_001356325.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRZ1	ENST00000393386.7	TSL:1 MANE Select	c.504A>C	p.Glu168Asp	missense	Exon 5 of 30	ENSP00000377047.2	P23471-1
	PTPRZ1	ENST00000449182.1	TSL:1	c.504A>C	p.Glu168Asp	missense	Exon 5 of 29	ENSP00000410000.1	P23471-3
	PTPRZ1	ENST00000651863.1		c.504A>C	p.Glu168Asp	missense	Exon 5 of 31	ENSP00000498439.1	A0A494C087

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1456952 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724892

African (AFR) AF: 0.00 AC: 0 AN: 33420

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26012

East Asian (EAS) AF: 0.00 AC: 0 AN: 39568

South Asian (SAS) AF: 0.00 AC: 0 AN: 85796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5210

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108940

Other (OTH) AF: 0.00 AC: 0 AN: 60106

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.0032
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.78
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.013	D
Polyphen		0.89	P
Vest4		0.23
MutPred		0.72		Loss of sheet (P = 0.0817)
MVP		0.31
MPC		0.088
ClinPred		0.78	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.74
Mutation Taster		=47/53	disease causing

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: rs1257076255; hg19: chr7-121616274;