chr12-80444396-A-C

Variant names:

• chr12-80444396-A-C
• rs1046355086
• NM_001145026.2:c.51A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001145026.2(PTPRQ):​c.51A>C​(p.Thr17Thr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000383 in 1,304,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: PTPRQ NM_001145026.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.59
• 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 12-80444396-A-C is Benign according to our data. Variant chr12-80444396-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2672512.Status of the report is criteria_provided_single_submitter, 1 stars.

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.51A>C	p.Thr17Thr	synonymous	Exon 1 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.51A>C	p.Thr17Thr	synonymous	Exon 1 of 45	ENSP00000495607.1	A0A087WZU1
	PTPRQ	ENST00000616559.4	TSL:5	c.181-345A>C		intron	N/A	ENSP00000483259.1	A0A087X0B9
	PTPRQ	ENST00000547376.5	TSL:5	c.919-345A>C		intron	N/A	ENSP00000448844.1	F8VXI2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000383 AC: 5 AN: 1304714 Hom.: 0 Cov.: 22 AF XY: 0.00000309 AC XY: 2 AN XY: 648098

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 27914

American (AMR) AF: 0.00 AC: 0 AN: 35226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24490

East Asian (EAS) AF: 0.00 AC: 0 AN: 35160

South Asian (SAS) AF: 0.00 AC: 0 AN: 76678

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49166

Middle Eastern (MID) AF: 0.000366 AC: 2 AN: 5468

European-Non Finnish (NFE) AF: 0.00000201 AC: 2 AN: 996086

Other (OTH) AF: 0.0000183 AC: 1 AN: 54526

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000516738), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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_noAF	Benign	-0.59
CADD	Benign	9.2
DANN	Benign	0.77
PhyloP100		3.6
PromoterAI		-0.0060	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1046355086; hg19: chr12-80838176;