12-70745884-T-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002849.4(PTPRR):​c.941A>C​(p.Lys314Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPRR NM_002849.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.831
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11796892).

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>C	p.Lys314Thr	missense	Exon 6 of 14	NP_002840.2
	PTPRR	NM_001207015.2		c.605A>C	p.Lys202Thr	missense	Exon 5 of 13	NP_001193944.1
	PTPRR	NM_001207016.1		c.323A>C	p.Lys108Thr	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>C	p.Lys314Thr	missense	Exon 6 of 14	ENSP00000283228.2
	PTPRR	ENST00000378778.5	TSL:1	c.323A>C	p.Lys108Thr	missense	Exon 3 of 11	ENSP00000368054.1
	PTPRR	ENST00000440835.6	TSL:1	c.206A>C	p.Lys69Thr	missense	Exon 2 of 10	ENSP00000391750.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461808 Hom.: 0 Cov.: 67 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111966

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.83
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.13
Sift	Benign	0.32	T
Sift4G	Benign	0.53	T
Polyphen		0.019	B
Vest4		0.51
MutPred		0.36		Loss of ubiquitination at K314 (P = 0.0037)
MVP		0.43
MPC		0.14
ClinPred		0.20	T
GERP RS		0.59
Varity_R		0.053
gMVP		0.36
Mutation Taster		=86/14	polymorphism

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: rs3803036; hg19: chr12-71139664;