12-80670365-C-G

Variant names:

• chr12-80670365-C-G
• rs1445287184
• NM_001145026.2:c.6475C>G

Variant summary

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

The NM_001145026.2(PTPRQ):​c.6475C>G​(p.Arg2159Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,606 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2159Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PTPRQ NM_001145026.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.939
• Publications: 0 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 73

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000304204 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.6475C>G	p.Arg2159Gly	missense	Exon 42 of 45	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000644991.3	MANE Select	c.6475C>G	p.Arg2159Gly	missense	Exon 42 of 45	ENSP00000495607.1	A0A087WZU1
	PTPRQ	ENST00000616559.4	TSL:5	c.6574C>G	p.Arg2192Gly	missense	Exon 42 of 45	ENSP00000483259.1	A0A087X0B9
	ENSG00000304204	ENST00000801015.1		n.100+36744G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398606 Hom.: 0 Cov.: 30 AF XY: 0.00000290 AC XY: 2 AN XY: 689816

African (AFR) AF: 0.00 AC: 0 AN: 31526

American (AMR) AF: 0.00 AC: 0 AN: 35652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35720

South Asian (SAS) AF: 0.00 AC: 0 AN: 79162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1078442

Other (OTH) AF: 0.00 AC: 0 AN: 57978

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.48	N
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.42	T
MetaSVM	Uncertain	-0.23	T
PhyloP100		0.94
PrimateAI	Benign	0.27	T
Sift4G	Uncertain	0.0040	D
Vest4		0.69
MutPred		0.72		Gain of catalytic residue at Q2193 (P = 0)
MVP		0.26
ClinPred		0.87	D
GERP RS		1.7
gMVP		0.50
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs1445287184; hg19: chr12-81064144;