rs761886073

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-121968055-C-A
• chr7-121968055-C-T

Variant summary

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

The NM_002851.3(PTPRZ1):​c.229C>A​(p.Leu77Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000811 in 1,602,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. L77F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000087 (0 hom.)
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35727692).

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>A	p.Leu77Ile	missense	Exon 3 of 30	NP_002842.2	P23471-1
	PTPRZ1	NM_001369395.1		c.229C>A	p.Leu77Ile	missense	Exon 3 of 29	NP_001356324.1	P23471-2
	PTPRZ1	NM_001369396.1		c.187C>A	p.Leu63Ile	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>A	p.Leu77Ile	missense	Exon 3 of 30	ENSP00000377047.2	P23471-1
	PTPRZ1	ENST00000449182.1	TSL:1	c.229C>A	p.Leu77Ile	missense	Exon 3 of 29	ENSP00000410000.1	P23471-3
	PTPRZ1	ENST00000651863.1		c.229C>A	p.Leu77Ile	missense	Exon 3 of 31	ENSP00000498439.1	A0A494C087

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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

GnomAD2 exomes AF: 0.0000606 AC: 15 AN: 247506 AF XY: 0.0000822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000120

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000869 AC: 126 AN: 1450092 Hom.: 0 Cov.: 30 AF XY: 0.0000928 AC XY: 67 AN XY: 721922

African (AFR) AF: 0.00 AC: 0 AN: 33124

American (AMR) AF: 0.0000454 AC: 2 AN: 44046

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.00 AC: 0 AN: 39370

South Asian (SAS) AF: 0.00 AC: 0 AN: 85024

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.000102 AC: 112 AN: 1103376

Other (OTH) AF: 0.000167 AC: 10 AN: 60008

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152146 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74332

African (AFR) AF: 0.0000241 AC: 1 AN: 41450

American (AMR) AF: 0.0000655 AC: 1 AN: 15258

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

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

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000302

ExAC AF: 0.0000659 AC: 8

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.31
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.36	T
MetaSVM	Uncertain	-0.064	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		4.1
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.78	N
REVEL	Uncertain	0.51
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.039	D
Polyphen		0.94	P
Vest4		0.46
MVP		0.38
MPC		0.52
ClinPred		0.21	T
GERP RS		5.7
Varity_R		0.73
gMVP		0.72
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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; COSMIC: COSV101100836; COSMIC: COSV101100836;