chr12-70745884-T-C

Variant names:

• chr12-70745884-T-C
• rs3803036
• NM_002849.4:c.941A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002849.4(PTPRR):​c.941A>G​(p.Lys314Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.766 in 1,613,718 control chromosomes in the GnomAD database, including 480,733 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 0.68 (37704 hom., cov: 30)
  • Exomes 𝑓: 0.78 (443029 hom.)
• Consequence: PTPRR NM_002849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 43 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=6.953038E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

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.941A>G	p.Lys314Arg	missense	Exon 6 of 14	NP_002840.2
	PTPRR	NM_001207015.2		c.605A>G	p.Lys202Arg	missense	Exon 5 of 13	NP_001193944.1
	PTPRR	NM_001207016.1		c.323A>G	p.Lys108Arg	missense	Exon 3 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.941A>G	p.Lys314Arg	missense	Exon 6 of 14	ENSP00000283228.2
	PTPRR	ENST00000378778.5	TSL:1	c.323A>G	p.Lys108Arg	missense	Exon 3 of 11	ENSP00000368054.1
	PTPRR	ENST00000440835.6	TSL:1	c.206A>G	p.Lys69Arg	missense	Exon 2 of 10	ENSP00000391750.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103074 AN: 151840 Hom.: 37680 Cov.: 30

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.773 AC: 194147 AN: 251102 AF XY: 0.775

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.840

Gnomad ASJ exome AF: 0.788

Gnomad EAS exome AF: 0.923

Gnomad FIN exome AF: 0.811

Gnomad NFE exome AF: 0.786

Gnomad OTH exome AF: 0.777

GnomAD4 exome AF: 0.775 AC: 1132985 AN: 1461762 Hom.: 443029 Cov.: 67 AF XY: 0.776 AC XY: 563962 AN XY: 727180

African (AFR) AF: 0.354 AC: 11841 AN: 33476

American (AMR) AF: 0.835 AC: 37331 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 20458 AN: 26136

East Asian (EAS) AF: 0.924 AC: 36667 AN: 39692

South Asian (SAS) AF: 0.750 AC: 64695 AN: 86258

European-Finnish (FIN) AF: 0.808 AC: 43153 AN: 53406

Middle Eastern (MID) AF: 0.730 AC: 4207 AN: 5766

European-Non Finnish (NFE) AF: 0.782 AC: 869047 AN: 1111924

Other (OTH) AF: 0.755 AC: 45586 AN: 60390

GnomAD4 genome AF: 0.679 AC: 103135 AN: 151956 Hom.: 37704 Cov.: 30 AF XY: 0.684 AC XY: 50772 AN XY: 74252

African (AFR) AF: 0.376 AC: 15553 AN: 41386

American (AMR) AF: 0.794 AC: 12130 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2738 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4757 AN: 5156

South Asian (SAS) AF: 0.765 AC: 3673 AN: 4804

European-Finnish (FIN) AF: 0.807 AC: 8540 AN: 10588

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53306 AN: 67964

Other (OTH) AF: 0.712 AC: 1500 AN: 2108

Alfa AF: 0.756 Hom.: 197752

Bravo AF: 0.666

TwinsUK AF: 0.772 AC: 2862

ALSPAC AF: 0.775 AC: 2985

ESP6500AA AF: 0.380 AC: 1674

ESP6500EA AF: 0.785 AC: 6753

ExAC AF: 0.762 AC: 92520

Asia WGS AF: 0.829 AC: 2883 AN: 3478

EpiCase AF: 0.777

EpiControl AF: 0.782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.60
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.56	T
MetaRNN	Benign	7.0e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	N
PhyloP100		0.83
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.031
Sift	Benign	0.61	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.090
MPC		0.093
ClinPred		0.0023	T
GERP RS		0.59
Varity_R		0.027
gMVP		0.25
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3803036; hg19: chr12-71139664; COSMIC: COSV51736040;