chr11-18744101-A-G

Position:

• chr11-18744101-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000358540.7(PTPN5):​c.196T>C​(p.Ser66Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,611,294 control chromosomes in the GnomAD database, including 167 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0088 (11 hom., cov: 32)
  • Exomes 𝑓: 0.012 (156 hom.)
• Consequence: PTPN5 ENST00000358540.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0043842196).
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN5	NM_006906.2	c.196T>C	p.Ser66Pro	missense_variant	4/15	ENST00000358540.7	NP_008837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN5	ENST00000358540.7	c.196T>C	p.Ser66Pro	missense_variant	4/15	1	NM_006906.2	ENSP00000351342
PTPN5	ENST00000396168.1	c.124T>C	p.Ser42Pro	missense_variant	3/14	1		ENSP00000379471	P1
PTPN5	ENST00000396170.5	c.196T>C	p.Ser66Pro	missense_variant	4/15	2		ENSP00000379473
PTPN5	ENST00000496201.2	n.243T>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 1341 AN: 152104 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00250

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0142

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00778 AC: 1920 AN: 246726 Hom.: 14 AF XY: 0.00802 AC XY: 1073 AN XY: 133712

Gnomad AFR exome AF: 0.00199

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00140

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00273

Gnomad FIN exome AF: 0.0120

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.00628

GnomAD4 exome AF: 0.0124 AC: 18165 AN: 1459072 Hom.: 156 Cov.: 31 AF XY: 0.0121 AC XY: 8798 AN XY: 725928

Gnomad4 AFR exome AF: 0.00180

Gnomad4 AMR exome AF: 0.00265

Gnomad4 ASJ exome AF: 0.00207

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00262

Gnomad4 FIN exome AF: 0.0112

Gnomad4 NFE exome AF: 0.0149

Gnomad4 OTH exome AF: 0.00961

GnomAD4 genome AF: 0.00879 AC: 1338 AN: 152222 Hom.: 11 Cov.: 32 AF XY: 0.00848 AC XY: 631 AN XY: 74416

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00614

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0142

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.0121 Hom.: 15

Bravo AF: 0.00804

TwinsUK AF: 0.0189 AC: 70

ALSPAC AF: 0.0163 AC: 63

ESP6500AA AF: 0.00318 AC: 14

ESP6500EA AF: 0.0129 AC: 111

ExAC AF: 0.00727 AC: 883

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.063	T;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.60	T;T;T
MetaRNN	Benign	0.0044	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.69	N;N;.
MutationTaster	Benign	0.98	N;N;N;N;N
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.074
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.082	T;D;T
Polyphen		0.0010	B;.;.
Vest4		0.33
MVP		0.32
MPC		0.37
ClinPred		0.012	T
GERP RS		-0.96
Varity_R		0.073
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs56234898; hg19: chr11-18765648; COSMIC: COSV62124794; COSMIC: COSV62124794;