chr12-80444141-T-A

Variant names:

• chr12-80444141-T-A
• rs1331555937
• ENST00000616559.4:c.180+229T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000551573.5(PTPRQ):​c.708+229T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 147,002 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (7 hom., cov: 29)
  • Exomes 𝑓: 0.00050 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPRQ ENST00000551573.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0790
• 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, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• hearing loss, autosomal recessive

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

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 12-80444141-T-A is Benign according to our data. Variant chr12-80444141-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1204969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00347 (510/147002) while in subpopulation AFR AF = 0.0123 (499/40592). AF 95% confidence interval is 0.0114. There are 7 homozygotes in GnomAd4. There are 235 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 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
	PTPRQ	NM_001145026.2	MANE Select	c.-205T>A		upstream_gene	N/A	NP_001138498.1	A0A087WZU1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRQ	ENST00000616559.4	TSL:5	c.180+229T>A		intron	N/A	ENSP00000483259.1	A0A087X0B9
	PTPRQ	ENST00000547376.5	TSL:5	c.918+229T>A		intron	N/A	ENSP00000448844.1	F8VXI2
	PTPRQ	ENST00000551042.5	TSL:5	c.660+229T>A		intron	N/A	ENSP00000447522.1	F8W122

Frequencies

GnomAD3 genomes AF: 0.00342 AC: 503 AN: 146884 Hom.: 7 Cov.: 29

Gnomad AFR AF: 0.0122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000611

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00101

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000501 AC: 78 AN: 155744 Hom.: 3 Cov.: 0 AF XY: 0.000405 AC XY: 34 AN XY: 83908

African (AFR) AF: 0.0203 AC: 62 AN: 3048

American (AMR) AF: 0.00103 AC: 5 AN: 4860

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3850

East Asian (EAS) AF: 0.00 AC: 0 AN: 7570

South Asian (SAS) AF: 0.0000827 AC: 2 AN: 24174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 588

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 93722

Other (OTH) AF: 0.00106 AC: 9 AN: 8510

GnomAD4 genome AF: 0.00347 AC: 510 AN: 147002 Hom.: 7 Cov.: 29 AF XY: 0.00328 AC XY: 235 AN XY: 71718

African (AFR) AF: 0.0123 AC: 499 AN: 40592

American (AMR) AF: 0.000610 AC: 9 AN: 14754

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5134

South Asian (SAS) AF: 0.00 AC: 0 AN: 4630

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65576

Other (OTH) AF: 0.000995 AC: 2 AN: 2010

Alfa AF: 0.00287 Hom.: 0

ClinVar

ClinVar submissions as Germline

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_noAF	Benign	-0.46
CADD	Benign	6.6
DANN	Benign	0.83
PhyloP100		-0.079
PromoterAI		0.063	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1331555937; hg19: chr12-80837921;