11-18729719-C-G

Variant names:

• chr11-18729719-C-G
• NM_006906.2:c.1429G>C

Variant summary

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

The NM_006906.2(PTPN5):​c.1429G>C​(p.Glu477Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 4.06
• Publications: 0 publications found

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

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=0.34061223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006906.2. 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
	PTPN5	NM_006906.2	MANE Select	c.1429G>C	p.Glu477Gln	missense	Exon 13 of 15	NP_008837.1	P54829-1
	PTPN5	NM_032781.4		c.1429G>C	p.Glu477Gln	missense	Exon 13 of 15	NP_116170.3
	PTPN5	NM_001278238.2		c.1357G>C	p.Glu453Gln	missense	Exon 12 of 14	NP_001265167.1	P54829-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPN5	ENST00000358540.7	TSL:1 MANE Select	c.1429G>C	p.Glu477Gln	missense	Exon 13 of 15	ENSP00000351342.2	P54829-1
	PTPN5	ENST00000396168.1	TSL:1	c.1357G>C	p.Glu453Gln	missense	Exon 12 of 14	ENSP00000379471.1	P54829-3
	PTPN5	ENST00000935333.1		c.1504G>C	p.Glu502Gln	missense	Exon 14 of 16	ENSP00000605392.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.22
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.025	D
Sift4G	Benign	0.20	T
Polyphen		0.63	P
Vest4		0.25
MutPred		0.52		Loss of disorder (P = 0.126)
MVP		0.91
MPC		0.69
ClinPred		0.93	D
GERP RS		4.3
Varity_R		0.24
gMVP		0.64
Mutation Taster		=70/30	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

hg19: chr11-18751266;