7-121997991-C-A

Position:

• chr7-121997991-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002851.3(PTPRZ1):​c.1225C>A​(p.Pro409Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PTPRZ1 NM_002851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.51

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRZ1	NM_002851.3	c.1225C>A	p.Pro409Thr	missense_variant	10/30	ENST00000393386.7	NP_002842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRZ1	ENST00000393386.7	c.1225C>A	p.Pro409Thr	missense_variant	10/30	1	NM_002851.3	ENSP00000377047.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jul 09, 2024

The c.1225C>A (p.P409T) alteration is located in exon 10 (coding exon 10) of the PTPRZ1 gene. This alteration results from a C to A substitution at nucleotide position 1225, causing the proline (P) at amino acid position 409 to be replaced by a threonine (T). 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	0.28
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Uncertain	0.53	D;.
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.50	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.16
Sift	Benign	0.15	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.95	P;.
Vest4		0.75
MutPred		0.43		Gain of glycosylation at P409 (P = 0.0104);Gain of glycosylation at P409 (P = 0.0104);
MVP		0.29
MPC		0.53
ClinPred		0.93	D
GERP RS		5.5
Varity_R		0.11
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-121638045;