NM_032611.3:c.199-5C>T

Variant names:

• chr8-141426934-C-T
• rs74648509
• NM_032611.3:c.199-5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032611.3(PTP4A3):​c.199-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00598 in 1,611,176 control chromosomes in the GnomAD database, including 489 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (238 hom., cov: 33)
  • Exomes 𝑓: 0.0033 (251 hom.)
• Consequence: PTP4A3 NM_032611.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001532
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.93
• Publications: 0 publications found

Genes affected

PTP4A3 (HGNC:9636): (protein tyrosine phosphatase 4A3) This gene encodes a member of the protein-tyrosine phosphatase family. Protein tyrosine phosphatases are cell signaling molecules that play regulatory roles in a variety of cellular processes. Studies of this class of protein tyrosine phosphatase in mice demonstrates that they are prenylated in vivo, suggesting their association with cell plasma membrane. The encoded protein may enhance cell proliferation, and overexpression of this gene has been implicated in tumor metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-141426934-C-T is Benign according to our data. Variant chr8-141426934-C-T is described in ClinVar as Benign. ClinVar VariationId is 769747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032611.3. 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
	PTP4A3	NM_032611.3	MANE Select	c.199-5C>T		splice_region intron	N/A	NP_116000.1	O75365-1
	PTP4A3	NM_001438241.1		c.199-5C>T		splice_region intron	N/A	NP_001425170.1
	PTP4A3	NM_001438242.1		c.199-5C>T		splice_region intron	N/A	NP_001425171.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTP4A3	ENST00000521578.6	TSL:5 MANE Select	c.199-5C>T		splice_region intron	N/A	ENSP00000428976.1	O75365-1
	PTP4A3	ENST00000329397.6	TSL:1	c.199-5C>T		splice_region intron	N/A	ENSP00000332274.1	O75365-1
	PTP4A3	ENST00000349124.3	TSL:1	c.199-5C>T		splice_region intron	N/A	ENSP00000331730.2	O75365-1

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4827 AN: 152214 Hom.: 239 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.00812 AC: 2001 AN: 246578 AF XY: 0.00597

Gnomad AFR exome AF: 0.111

Gnomad AMR exome AF: 0.00458

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.00363

GnomAD4 exome AF: 0.00329 AC: 4800 AN: 1458844 Hom.: 251 Cov.: 31 AF XY: 0.00274 AC XY: 1985 AN XY: 725770

African (AFR) AF: 0.120 AC: 4033 AN: 33474

American (AMR) AF: 0.00521 AC: 233 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50956

Middle Eastern (MID) AF: 0.00608 AC: 35 AN: 5760

European-Non Finnish (NFE) AF: 0.0000900 AC: 100 AN: 1111688

Other (OTH) AF: 0.00636 AC: 384 AN: 60338

GnomAD4 genome AF: 0.0317 AC: 4829 AN: 152332 Hom.: 238 Cov.: 33 AF XY: 0.0305 AC XY: 2271 AN XY: 74482

African (AFR) AF: 0.110 AC: 4565 AN: 41564

American (AMR) AF: 0.0127 AC: 195 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68034

Other (OTH) AF: 0.0232 AC: 49 AN: 2112

Alfa AF: 0.0127 Hom.: 57

Bravo AF: 0.0352

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.029
DANN	Benign	0.73
PhyloP100		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0040
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: rs74648509; hg19: chr8-142437034;