3-47381160-T-C

Position:

• chr3-47381160-T-C

Variant summary

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

The NM_015466.4(PTPN23):​c.64T>C​(p.Phe22Leu) 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPN23 NM_015466.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.50

Genes affected

PTPN23 (HGNC:14406): (protein tyrosine phosphatase non-receptor type 23) This gene encodes a member of the non-receptor type protein-tyrosine phosphatase family. The encoded protein may be involved in the regulation of small nuclear ribonucleo protein assembly and pre-mRNA splicing by modifying the survival motor neuron (SMN) complex. The encoded protein additionally plays a role in ciliogenesis and is part of endosomal sorting complex required for transport (ESCRT) pathways. This gene may serve a tumor suppressor function. [provided by RefSeq, Jul 2016]

PTPN23 (HGNC:):

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
PTPN23	NM_015466.4	c.64T>C	p.Phe22Leu	missense_variant	1/25	ENST00000265562.5	NP_056281.1
PTPN23	XM_005265031.3	c.64T>C	p.Phe22Leu	missense_variant	1/25		XP_005265088.2
PTPN23	NM_001304482.2	c.-187T>C		5_prime_UTR_variant	1/24		NP_001291411.1
PTPN23-DT	NR_185912.1	n.333A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN23	ENST00000265562.5	c.64T>C	p.Phe22Leu	missense_variant	1/25	1	NM_015466.4	ENSP00000265562.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1437246 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712852

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 13, 2022

Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with PTPN23-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 22 of the PTPN23 protein (p.Phe22Leu). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.087	T;T
Eigen	Benign	-0.040
Eigen_PC	Benign	0.060
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.082	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.31	.;N
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.15
Sift	Benign	0.63	T;D
Sift4G	Benign	0.11	T;D
Polyphen		0.23	.;B
Vest4		0.45
MutPred		0.74		Loss of methylation at K27 (P = 0.0766);Loss of methylation at K27 (P = 0.0766);
MVP		0.35
MPC		0.52
ClinPred		0.92	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.79
gMVP		0.49

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: chr3-47422650;