12-70754214-C-T

Variant names:

• chr12-70754214-C-T
• rs73341069
• NM_002849.4:c.715G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002849.4(PTPRR):​c.715G>A​(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 1,613,444 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.012 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (36 hom.)
• Consequence: PTPRR NM_002849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 7 publications found

Genes affected

PTPRR (HGNC:9680): (protein tyrosine phosphatase receptor type R) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. Silencing of this gene has been associated with colorectal cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares a symbol (PTPRQ) with another gene, protein tyrosine phosphatase, receptor type, Q (GeneID 374462), which is also located on chromosome 12. [provided by RefSeq, May 2011]

ENSG00000307941 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030323863).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1782/152232) while in subpopulation AFR AF = 0.0406 (1687/41524). AF 95% confidence interval is 0.039. There are 39 homozygotes in GnomAd4. There are 838 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002849.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRR	NM_002849.4	MANE Select	c.715G>A	p.Val239Ile	missense	Exon 5 of 14	NP_002840.2
	PTPRR	NM_001207015.2		c.379G>A	p.Val127Ile	missense	Exon 4 of 13	NP_001193944.1
	PTPRR	NM_001207016.1		c.97G>A	p.Val33Ile	missense	Exon 2 of 11	NP_001193945.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRR	ENST00000283228.7	TSL:1 MANE Select	c.715G>A	p.Val239Ile	missense	Exon 5 of 14	ENSP00000283228.2
	PTPRR	ENST00000378778.5	TSL:1	c.97G>A	p.Val33Ile	missense	Exon 2 of 11	ENSP00000368054.1
	PTPRR	ENST00000551219.5	TSL:1	n.-302G>A		non_coding_transcript_exon	Exon 1 of 11	ENSP00000448049.1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1772 AN: 152114 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00329 AC: 822 AN: 250046 AF XY: 0.00268

Gnomad AFR exome AF: 0.0429

Gnomad AMR exome AF: 0.00273

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000177

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00125 AC: 1827 AN: 1461212 Hom.: 36 Cov.: 31 AF XY: 0.00113 AC XY: 821 AN XY: 726880

African (AFR) AF: 0.0400 AC: 1338 AN: 33456

American (AMR) AF: 0.00300 AC: 134 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53302

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5758

European-Non Finnish (NFE) AF: 0.0000980 AC: 109 AN: 1111716

Other (OTH) AF: 0.00355 AC: 214 AN: 60356

GnomAD4 genome AF: 0.0117 AC: 1782 AN: 152232 Hom.: 39 Cov.: 32 AF XY: 0.0113 AC XY: 838 AN XY: 74414

African (AFR) AF: 0.0406 AC: 1687 AN: 41524

American (AMR) AF: 0.00406 AC: 62 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68014

Other (OTH) AF: 0.00710 AC: 15 AN: 2112

Alfa AF: 0.00420 Hom.: 20

Bravo AF: 0.0133

ESP6500AA AF: 0.0381 AC: 168

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00409 AC: 497

Asia WGS AF: 0.00289 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		1.3
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.062
Sift	Benign	0.50	T
Sift4G	Benign	0.64	T
Polyphen		0.0020	B
Vest4		0.21
MVP		0.46
MPC		0.092
ClinPred		0.0075	T
GERP RS		0.29
PromoterAI		-0.019	Neutral
Varity_R		0.036
gMVP		0.33
Mutation Taster		=86/14	polymorphism (auto)

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: rs73341069; hg19: chr12-71147994;