9-137192572-TTCCTCCTCCTCCTCCTCC-TTCCTCCTCCTCCTCC

Position:

• chr9-137192572-TTCCTCCTCCTCCTCCTCC-TTCCTCCTCCTCCTCC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001128228.3(TPRN):​c.1842_1844del​(p.Glu621del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,564,720 control chromosomes in the GnomAD database, including 14 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (9 hom.)
• Consequence: TPRN NM_001128228.3 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.164

Genes affected

TPRN (HGNC:26894): (taperin) This locus encodes a sensory epithelial protein. It was defined by linkage analysis in three Pakistani families to lie between D9S1818 (centromeric) and D9SH6 (telomeric). Mutations at this locus have been associated with autosomal recessive deafness. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 9-137192572-TTCC-T is Benign according to our data. Variant chr9-137192572-TTCC-T is described in ClinVar as [Benign]. Clinvar id is 165579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-137192572-TTCC-T is described in Lovd as [Benign]. Variant chr9-137192572-TTCC-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00577 (873/151212) while in subpopulation AFR AF= 0.0173 (714/41244). AF 95% confidence interval is 0.0163. There are 5 homozygotes in gnomad4. There are 422 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.1842_1844del	p.Glu621del	inframe_deletion	2/4	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6	c.1842_1844del	p.Glu621del	inframe_deletion	2/4	1	NM_001128228.3	ENSP00000387100	P1
TPRN	ENST00000477345.1	n.2563_2565del		non_coding_transcript_exon_variant	1/3	1
TPRN	ENST00000333046.8	c.1236_1238del	p.Glu419del	inframe_deletion	2/3	2		ENSP00000327617

Frequencies

GnomAD3 genomes AF: 0.00578 AC: 873 AN: 151102 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00264

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00158

Gnomad SAS AF: 0.00522

Gnomad FIN AF: 0.0000958

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00117

Gnomad OTH AF: 0.00338

GnomAD3 exomes AF: 0.00610 AC: 1280 AN: 209928 Hom.: 1 AF XY: 0.00600 AC XY: 683 AN XY: 113872

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00437

Gnomad SAS exome AF: 0.00794

Gnomad FIN exome AF: 0.00442

Gnomad NFE exome AF: 0.00498

Gnomad OTH exome AF: 0.00472

GnomAD4 exome AF: 0.00200 AC: 2832 AN: 1413508 Hom.: 9 AF XY: 0.00215 AC XY: 1507 AN XY: 701808

Gnomad4 AFR exome AF: 0.0191

Gnomad4 AMR exome AF: 0.00347

Gnomad4 ASJ exome AF: 0.000399

Gnomad4 EAS exome AF: 0.00149

Gnomad4 SAS exome AF: 0.00631

Gnomad4 FIN exome AF: 0.00227

Gnomad4 NFE exome AF: 0.00108

Gnomad4 OTH exome AF: 0.00298

GnomAD4 genome AF: 0.00577 AC: 873 AN: 151212 Hom.: 5 Cov.: 33 AF XY: 0.00571 AC XY: 422 AN XY: 73880

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.00257

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00158

Gnomad4 SAS AF: 0.00522

Gnomad4 FIN AF: 0.0000958

Gnomad4 NFE AF: 0.00117

Gnomad4 OTH AF: 0.00334

Bravo AF: 0.00701

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Feb 15, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 11, 2013

Glu621del in Exon 2 of TPRN: This variant is not expected to have clinical signi ficance because it has been identified in 5.7% (455/8007) of European American c hromosomes and 6.5% (264/4126) of African American chromosomes by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs77086130 ). -

Autosomal recessive nonsyndromic hearing loss 79 Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs376810326; hg19: chr9-140087024;