chr7-121968055-C-T

Position:

• chr7-121968055-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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 (★).

• 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

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.229C>T	p.Leu77Phe	missense_variant	3/30	ENST00000393386.7	NP_002842.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRZ1	ENST00000393386.7	c.229C>T	p.Leu77Phe	missense_variant	3/30	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 16, 2021

The c.229C>T (p.L77F) alteration is located in exon 3 (coding exon 3) of the PTPRZ1 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the leucine (L) at amino acid position 77 to be replaced by a phenylalanine (F). 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	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;T
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.81	N;N
REVEL	Uncertain	0.37
Sift	Uncertain	0.023	D;T
Sift4G	Benign	0.47	T;T
Polyphen		0.80	P;.
Vest4		0.57
MutPred		0.83		Gain of methylation at K78 (P = 0.0299);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-121608109;