NM_002851.3:c.229C>T

Variant names:

• chr7-121968055-C-T
• rs761886073
• NM_002851.3:c.229C>T

Variant summary

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

The NM_002851.3(PTPRZ1):​c.229C>T​(p.Leu77Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L77I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRZ1 NM_002851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.12
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.229C>T	p.Leu77Phe	missense	Exon 3 of 30	NP_002842.2	P23471-1
	PTPRZ1	NM_001369395.1		c.229C>T	p.Leu77Phe	missense	Exon 3 of 29	NP_001356324.1	P23471-2
	PTPRZ1	NM_001369396.1		c.187C>T	p.Leu63Phe	missense	Exon 4 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.229C>T	p.Leu77Phe	missense	Exon 3 of 30	ENSP00000377047.2	P23471-1
	PTPRZ1	ENST00000449182.1	TSL:1	c.229C>T	p.Leu77Phe	missense	Exon 3 of 29	ENSP00000410000.1	P23471-3
	PTPRZ1	ENST00000651863.1		c.229C>T	p.Leu77Phe	missense	Exon 3 of 31	ENSP00000498439.1	A0A494C087

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	Uncertain	0.45
BayesDel_addAF	Benign	0.0038	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.81	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.023	D
Sift4G	Benign	0.47	T
Polyphen		0.80	P
Vest4		0.57
MutPred		0.83		Gain of methylation at K78 (P = 0.0299)
MVP		0.14
MPC		0.52
ClinPred		0.84	D
GERP RS		5.7
Varity_R		0.43
gMVP		0.78
Mutation Taster		=76/24	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs761886073; hg19: chr7-121608109;