4-86689126-A-G

Variant names:

• chr4-86689126-A-G
• rs772538106
• NM_080683.3:c.482A>G

Variant summary

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

The NM_080683.3(PTPN13):​c.482A>G​(p.Asn161Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000034 (0 hom.)
• Consequence: PTPN13 NM_080683.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64
• Publications: 1 publications found

Genes affected

PTPN13 (HGNC:9646): (protein tyrosine phosphatase non-receptor type 13) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP is a large intracellular protein. It has a catalytic PTP domain at its C-terminus and two major structural domains: a region with five PDZ domains and a FERM domain that binds to plasma membrane and cytoskeletal elements. This PTP was found to interact with, and dephosphorylate, Fas receptor and IkappaBalpha through the PDZ domains. This suggests it has a role in Fas mediated programmed cell death. This PTP was also shown to interact with GTPase-activating protein, and thus may function as a regulator of Rho signaling pathways. Four alternatively spliced transcript variants, which encode distinct proteins, have been reported. [provided by RefSeq, Oct 2008]

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=0.18926689).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN13	NM_080683.3	c.482A>G	p.Asn161Ser	missense_variant	Exon 5 of 48	ENST00000411767.7	NP_542414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN13	ENST00000411767.7	c.482A>G	p.Asn161Ser	missense_variant	Exon 5 of 48	1	NM_080683.3	ENSP00000407249.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249156 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461368 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726990

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53402

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111576

Other (OTH) AF: 0.0000331 AC: 2 AN: 60364

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.482A>G (p.N161S) alteration is located in exon 5 (coding exon 4) of the PTPN13 gene. This alteration results from a A to G substitution at nucleotide position 482, causing the asparagine (N) at amino acid position 161 to be replaced by a serine (S). 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	0.063
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	.;.;.;.;T;.
Eigen	Benign	-0.14
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D;D;D;D;D;.
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.19	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;L;.;L;L;L
PhyloP100		2.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.35	N;N;N;N;N;N
REVEL	Benign	0.086
Sift	Benign	0.40	T;T;T;T;T;T
Sift4G	Benign	0.73	T;T;T;T;T;T
Polyphen		0.55	P;B;.;B;B;B
Vest4		0.36
MutPred		0.23		Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);Loss of solvent accessibility (P = 0.0058);
MVP		0.40
MPC		0.14
ClinPred		0.20	T
GERP RS		5.7
Varity_R		0.087
gMVP		0.11
Mutation Taster		=81/19	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: rs772538106; hg19: chr4-87610279;