12-80669077-G-C

Variant names:

• chr12-80669077-G-C
• NM_001145026.2:c.6263G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001145026.2(PTPRQ):​c.6263G>C​(p.Arg2088Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,558 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PTPRQ NM_001145026.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.54

Genes affected

PTPRQ (HGNC:9679): (protein tyrosine phosphatase receptor type Q) This locus encodes a member of the type III receptor-like protein-tyrosine phosphatase family. The encoded protein catalyzes the dephosphorylation of phosphotyrosine and phosphatidylinositol and plays roles in cellular proliferation and differentiation. Mutations at this locus have been linked to autosomal recessive deafness. [provided by RefSeq, Mar 2014]

LOC105369867 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.6263G>C	p.Arg2088Thr	missense_variant	Exon 40 of 45	ENST00000644991.3	NP_001138498.1
LOC105369867	XR_007063388.1	n.130+38032C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.6263G>C	p.Arg2088Thr	missense_variant	Exon 40 of 45		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.6362G>C	p.Arg2121Thr	missense_variant	Exon 40 of 45	5		ENSP00000483259.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398558 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689770

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D;.;D
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.92	D;D;D
MetaSVM	Uncertain	0.70	D
PrimateAI	Uncertain	0.69	T
Sift4G	Uncertain	0.0030	D;D;.
Vest4		0.93
MutPred		0.77		Gain of catalytic residue at M2122 (P = 0.0082);.;.;
MVP		0.28
ClinPred		0.98	D
GERP RS		5.6
gMVP		0.61

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-81062856;