rs367543226

Variant names:

• chr11-18733368-T-A
• rs367543226
• NM_006906.2:c.1085A>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18733368-T-A
• chr11-18733368-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006906.2(PTPN5):​c.1085A>T​(p.Tyr362Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y362C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PTPN5 NM_006906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.81
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.931

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.1085A>T	p.Tyr362Phe	missense	Exon 11 of 15	NP_008837.1	P54829-1
	PTPN5	NM_032781.4		c.1085A>T	p.Tyr362Phe	missense	Exon 11 of 15	NP_116170.3
	PTPN5	NM_001278238.2		c.1013A>T	p.Tyr338Phe	missense	Exon 10 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.1085A>T	p.Tyr362Phe	missense	Exon 11 of 15	ENSP00000351342.2	P54829-1
	PTPN5	ENST00000396168.1	TSL:1	c.1013A>T	p.Tyr338Phe	missense	Exon 10 of 14	ENSP00000379471.1	P54829-3
	PTPN5	ENST00000935333.1		c.1160A>T	p.Tyr387Phe	missense	Exon 12 of 16	ENSP00000605392.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.019	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.51	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.93	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.92	L
PhyloP100		7.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.34
Sift	Benign	0.071	T
Sift4G	Benign	0.13	T
Polyphen		0.86	P
Vest4		0.77
MutPred		0.85		Loss of ubiquitination at K367 (P = 0.0583)
MVP		0.59
MPC		0.96
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.59
gMVP		0.61
Mutation Taster		=34/66	disease causing

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: rs367543226; hg19: chr11-18754915;