rs1163042

Variant names:

• chr12-80669077-G-A
• rs1163042
• NM_001145026.2:c.6263G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80669077-G-A
• chr12-80669077-G-C
• chr12-80669077-G-T

Variant summary

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

The NM_001145026.2(PTPRQ):​c.6263G>A​(p.Arg2088Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00345 in 1,550,584 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (73 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (76 hom.)
• Consequence: PTPRQ NM_001145026.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.010514975).
• BP6: Variant 12-80669077-G-A is Benign according to our data. Variant chr12-80669077-G-A is described in ClinVar as [Benign]. Clinvar id is 586390.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRQ	NM_001145026.2	c.6263G>A	p.Arg2088Lys	missense_variant	Exon 40 of 45	ENST00000644991.3	NP_001138498.1
LOC105369867	XR_007063388.1	n.130+38032C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRQ	ENST00000644991.3	c.6263G>A	p.Arg2088Lys	missense_variant	Exon 40 of 45		NM_001145026.2	ENSP00000495607.1
PTPRQ	ENST00000616559.4	c.6362G>A	p.Arg2121Lys	missense_variant	Exon 40 of 45	5		ENSP00000483259.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2769 AN: 151924 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00676

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00385 AC: 609 AN: 158054 AF XY: 0.00282

Gnomad AFR exome AF: 0.0636

Gnomad AMR exome AF: 0.00259

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000179

Gnomad OTH exome AF: 0.00157

GnomAD4 exome AF: 0.00183 AC: 2562 AN: 1398542 Hom.: 76 Cov.: 31 AF XY: 0.00164 AC XY: 1134 AN XY: 689766

Gnomad4 AFR exome AF: 0.0681 AC: 2145 AN: 31500

Gnomad4 AMR exome AF: 0.00311 AC: 111 AN: 35680

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25114

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35672

Gnomad4 SAS exome AF: 0.0000632 AC: 5 AN: 79160

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 49472

Gnomad4 NFE exome AF: 0.0000659 AC: 71 AN: 1078204

Gnomad4 Remaining exome AF: 0.00379 AC: 220 AN: 58054

GnomAD4 genome AF: 0.0183 AC: 2781 AN: 152042 Hom.: 73 Cov.: 32 AF XY: 0.0173 AC XY: 1289 AN XY: 74314

Gnomad4 AFR AF: 0.0638 AC: 0.0637919 AN: 0.0637919

Gnomad4 AMR AF: 0.00675 AC: 0.00675144 AN: 0.00675144

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.0000736 AC: 0.0000736269 AN: 0.0000736269

Gnomad4 OTH AF: 0.0114 AC: 0.0113744 AN: 0.0113744

Alfa AF: 0.00631 Hom.: 88

Bravo AF: 0.0212

ESP6500AA AF: 0.0621 AC: 86

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00696 AC: 178

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 09, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.046	T;.;.
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;.;D
MetaRNN	Benign	0.011	T;T;T
MetaSVM	Benign	-0.31	T
PrimateAI	Uncertain	0.70	T
Sift4G	Uncertain	0.038	D;D;.
Vest4		0.81
MVP		0.17
ClinPred		0.033	T
GERP RS		5.6
gMVP		0.55
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

Publications

LitVar

Other links and lift over

dbSNP: rs1163042; hg19: chr12-81062856; COSMIC: COSV99030920;