rs144165124

Variant names:

• chr11-18729538-T-C
• rs144165124
• NM_006906.2:c.1519A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-18729538-T-C
• chr11-18729538-T-G

Variant summary

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

The NM_006906.2(PTPN5):​c.1519A>G​(p.Ile507Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,447,416 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. I507L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PTPN5 NM_006906.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.93
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPN5	NM_006906.2	c.1519A>G	p.Ile507Val	missense_variant	Exon 14 of 15	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.1519A>G	p.Ile507Val	missense_variant	Exon 14 of 15	1	NM_006906.2	ENSP00000351342.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447416 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 720856

African (AFR) AF: 0.00 AC: 0 AN: 33406

American (AMR) AF: 0.00 AC: 0 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5144

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107946

Other (OTH) AF: 0.00 AC: 0 AN: 60084

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	0.0054	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.23	.;T;T;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.70	D;D;D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	.;L;.;.;.
PhyloP100		5.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.82	N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.043	D;D;D;D;D
Sift4G	Uncertain	0.041	D;T;D;T;D
Polyphen		0.84	.;P;.;.;.
Vest4		0.71
MutPred		0.73		.;Gain of methylation at R502 (P = 0.2589);.;.;.;
MVP		0.65
MPC		0.91
ClinPred		0.92	D
GERP RS		4.3
Varity_R		0.29
gMVP		0.35
Mutation Taster		=56/44	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: rs144165124; hg19: chr11-18751085;