11-18733320-C-T

Variant names:

• chr11-18733320-C-T
• rs200575973
• NM_006906.2:c.1133G>A

Variant summary

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

The NM_006906.2(PTPN5):​c.1133G>A​(p.Ser378Asn) 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. 14/22 in silico tools predict a benign 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. S378T) 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: 5.00
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17536184).

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.1133G>A	p.Ser378Asn	missense	Exon 11 of 15	NP_008837.1	P54829-1
	PTPN5	NM_032781.4		c.1133G>A	p.Ser378Asn	missense	Exon 11 of 15	NP_116170.3
	PTPN5	NM_001278238.2		c.1061G>A	p.Ser354Asn	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.1133G>A	p.Ser378Asn	missense	Exon 11 of 15	ENSP00000351342.2	P54829-1
	PTPN5	ENST00000396168.1	TSL:1	c.1061G>A	p.Ser354Asn	missense	Exon 10 of 14	ENSP00000379471.1	P54829-3
	PTPN5	ENST00000935333.1		c.1208G>A	p.Ser403Asn	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	0.13
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	20
DANN	Benign	0.84
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.4	N
PhyloP100		5.0
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.11
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.24
MutPred		0.45		Loss of catalytic residue at S378 (P = 0.0381)
MVP		0.52
MPC		0.28
ClinPred		0.69	D
GERP RS		4.4
Varity_R		0.28
gMVP		0.43
Mutation Taster		=74/26	polymorphism

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: rs200575973; hg19: chr11-18754867; COSMIC: COSV62126884; COSMIC: COSV62126884;