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
• Publications: 4 publications found

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]

PTPRQ Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 84A

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• hearing loss, autosomal dominant 73

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000304204 (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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145026.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	NM_001145026.2	MANE Select	c.6263G>A	p.Arg2088Lys	missense	Exon 40 of 45	NP_001138498.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000644991.3	MANE Select	c.6263G>A	p.Arg2088Lys	missense	Exon 40 of 45	ENSP00000495607.1
	PTPRQ	ENST00000616559.4	TSL:5	c.6362G>A	p.Arg2121Lys	missense	Exon 40 of 45	ENSP00000483259.1
	ENSG00000304204	ENST00000801015.1		n.100+38032C>T		intron	N/A

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

African (AFR) AF: 0.0681 AC: 2145 AN: 31500

American (AMR) AF: 0.00311 AC: 111 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25114

East Asian (EAS) AF: 0.00 AC: 0 AN: 35672

South Asian (SAS) AF: 0.0000632 AC: 5 AN: 79160

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49472

Middle Eastern (MID) AF: 0.00176 AC: 10 AN: 5686

European-Non Finnish (NFE) AF: 0.0000659 AC: 71 AN: 1078204

Other (OTH) 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

African (AFR) AF: 0.0638 AC: 2648 AN: 41510

American (AMR) AF: 0.00675 AC: 103 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67910

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.31	T
PhyloP100		9.5
PrimateAI	Uncertain	0.70	T
Sift4G	Uncertain	0.038	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

Other links and lift over

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