chr11-18732600-A-G

Position:

• chr11-18732600-A-G

Variant summary

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

The NM_006906.2(PTPN5):​c.1321T>C​(p.Ser441Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: PTPN5 NM_006906.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.50

Genes affected

PTPN5 (HGNC:9657): (protein tyrosine phosphatase non-receptor type 5) Enables phosphotyrosine residue binding activity. Predicted to be involved in peptidyl-tyrosine dephosphorylation. Predicted to act upstream of or within protein dephosphorylation. Predicted to be located in nucleoplasm. Predicted to be integral component of membrane. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

IGSF22-AS1 (HGNC:55511): (IGSF22 antisense RNA 1)

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
PTPN5	NM_006906.2	c.1321T>C	p.Ser441Pro	missense_variant	12/15	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.1321T>C	p.Ser441Pro	missense_variant	12/15	1	NM_006906.2	ENSP00000351342
IGSF22-AS1	ENST00000527285.1	n.730-7824A>G		intron_variant, non_coding_transcript_variant		3

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

Aug 13, 2021

The c.1321T>C (p.S441P) alteration is located in exon 12 (coding exon 11) of the PTPN5 gene. This alteration results from a T to C substitution at nucleotide position 1321, causing the serine (S) at amino acid position 441 to be replaced by a proline (P). 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	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;T;.;.
Eigen	Benign	-0.0048
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.58	T;T;T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	1.8	.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Uncertain	0.58
Sift	Benign	0.031	D;D;D;D
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.010	.;B;.;.
Vest4		0.60
MutPred		0.50		.;Loss of sheet (P = 0.0817);.;.;
MVP		0.86
MPC		0.38
ClinPred		0.89	D
GERP RS		2.9
Varity_R		0.73
gMVP		0.75

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: chr11-18754147;