rs367543221

Variant names:

• chr11-18729473-C-A
• rs367543221
• NM_006906.2:c.1584G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-18729473-C-A
• chr11-18729473-C-G
• chr11-18729473-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_006906.2(PTPN5):​c.1584G>T​(p.Thr528Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T528T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PTPN5 NM_006906.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP7: Synonymous conserved (PhyloP=-1.15 with no splicing effect.

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.1584G>T	p.Thr528Thr	synonymous	Exon 14 of 15	NP_008837.1	P54829-1
	PTPN5	NM_032781.4		c.1584G>T	p.Thr528Thr	synonymous	Exon 14 of 15	NP_116170.3
	PTPN5	NM_001278238.2		c.1512G>T	p.Thr504Thr	synonymous	Exon 13 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.1584G>T	p.Thr528Thr	synonymous	Exon 14 of 15	ENSP00000351342.2	P54829-1
	PTPN5	ENST00000396168.1	TSL:1	c.1512G>T	p.Thr504Thr	synonymous	Exon 13 of 14	ENSP00000379471.1	P54829-3
	PTPN5	ENST00000935333.1		c.1659G>T	p.Thr553Thr	synonymous	Exon 15 of 16	ENSP00000605392.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412186 Hom.: 0 Cov.: 26 AF XY: 0.00000142 AC XY: 1 AN XY: 705612

African (AFR) AF: 0.00 AC: 0 AN: 32684

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4950

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1071564

Other (OTH) AF: 0.00 AC: 0 AN: 58904

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	3.9
DANN	Benign	0.86
PhyloP100		-1.2

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: rs367543221; hg19: chr11-18751020;