rs188234804

Variant names:

• chr12-80436384-T-C
• rs188234804
• ENST00000616559.4:c.19+1283T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-80436384-T-C
• chr12-80436384-T-A
• chr12-80436384-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000551573.5(PTPRQ):​c.547+1283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 370,210 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (3 hom.)
• Consequence: PTPRQ ENST00000551573.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.99
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.306464).
• BP6: Variant 12-80436384-T-C is Benign according to our data. Variant chr12-80436384-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2570840.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00504 (767/152268) while in subpopulation NFE AF = 0.00835 (568/68030). AF 95% confidence interval is 0.00778. There are 2 homozygotes in GnomAd4. There are 368 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR,SD,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551573.5. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000616559.4	TSL:5	c.19+1283T>C		intron	N/A	ENSP00000483259.1	A0A087X0B9
	PTPRQ	ENST00000547376.5	TSL:5	c.757+2T>C		splice_donor intron	N/A	ENSP00000448844.1	F8VXI2
	PTPRQ	ENST00000551042.5	TSL:5	c.499+1283T>C		intron	N/A	ENSP00000447522.1	F8W122

Frequencies

GnomAD3 genomes AF: 0.00504 AC: 767 AN: 152150 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00414

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00835

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00435 AC: 376 AN: 86394 AF XY: 0.00447

Gnomad AFR exome AF: 0.00113

Gnomad AMR exome AF: 0.00325

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00429

Gnomad NFE exome AF: 0.00837

Gnomad OTH exome AF: 0.00517

GnomAD4 exome AF: 0.00449 AC: 979 AN: 217942 Hom.: 3 Cov.: 0 AF XY: 0.00430 AC XY: 534 AN XY: 124296

African (AFR) AF: 0.00113 AC: 7 AN: 6172

American (AMR) AF: 0.00292 AC: 48 AN: 16432

Ashkenazi Jewish (ASJ) AF: 0.00211 AC: 15 AN: 7106

East Asian (EAS) AF: 0.00 AC: 0 AN: 8370

South Asian (SAS) AF: 0.000258 AC: 11 AN: 42586

European-Finnish (FIN) AF: 0.00449 AC: 39 AN: 8686

Middle Eastern (MID) AF: 0.000415 AC: 1 AN: 2412

European-Non Finnish (NFE) AF: 0.00689 AC: 798 AN: 115826

Other (OTH) AF: 0.00580 AC: 60 AN: 10352

GnomAD4 genome AF: 0.00504 AC: 767 AN: 152268 Hom.: 2 Cov.: 32 AF XY: 0.00494 AC XY: 368 AN XY: 74466

African (AFR) AF: 0.00193 AC: 80 AN: 41536

American (AMR) AF: 0.00288 AC: 44 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00414 AC: 44 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00835 AC: 568 AN: 68030

Other (OTH) AF: 0.00569 AC: 12 AN: 2110

Alfa AF: 0.00263 Hom.: 0

Bravo AF: 0.00508

TwinsUK AF: 0.00755 AC: 28

ALSPAC AF: 0.00804 AC: 31

ExAC AF: 0.00157 AC: 21

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.89
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		3.0
GERP RS		3.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs188234804; hg19: chr12-80830164; COSMIC: COSV101609045;