7-121968001-C-A

Variant names:

• chr7-121968001-C-A
• rs774322047
• NM_002851.3:c.175C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002851.3(PTPRZ1):​c.175C>A​(p.Pro59Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,442,134 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: not found (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: 6.23
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17877266).

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.175C>A	p.Pro59Thr	missense	Exon 3 of 30	NP_002842.2	P23471-1
	PTPRZ1	NM_001369395.1		c.175C>A	p.Pro59Thr	missense	Exon 3 of 29	NP_001356324.1	P23471-2
	PTPRZ1	NM_001369396.1		c.133C>A	p.Pro45Thr	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.175C>A	p.Pro59Thr	missense	Exon 3 of 30	ENSP00000377047.2	P23471-1
	PTPRZ1	ENST00000449182.1	TSL:1	c.175C>A	p.Pro59Thr	missense	Exon 3 of 29	ENSP00000410000.1	P23471-3
	PTPRZ1	ENST00000651863.1		c.175C>A	p.Pro59Thr	missense	Exon 3 of 31	ENSP00000498439.1	A0A494C087

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1442134 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 718166

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 32814

American (AMR) AF: 0.00 AC: 0 AN: 43744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25972

East Asian (EAS) AF: 0.00 AC: 0 AN: 39124

South Asian (SAS) AF: 0.00 AC: 0 AN: 84444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097136

Other (OTH) AF: 0.0000167 AC: 1 AN: 59804

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

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	0.14
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	0.41	N
PhyloP100		6.2
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.057
Sift	Uncertain	0.012	D
Sift4G	Benign	0.068	T
Polyphen		0.18	B
Vest4		0.22
MutPred		0.35		Loss of glycosylation at P59 (P = 0.0556)
MVP		0.15
MPC		0.43
ClinPred		0.72	D
GERP RS		5.5
Varity_R		0.30
gMVP		0.65
Mutation Taster		=57/43	polymorphism

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: rs774322047; hg19: chr7-121608055;