9-137192572-TTCCTCCTCCTCCTCCTCC-TTCCTCCTCCTCCTCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBS1BS2

The NM_001128228.3(TPRN):c.1842_1844delGGA(p.Glu615del) variant causes a disruptive 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 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.164

Publications

3 publications found

Variant links:

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]

TPRN Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 79
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TPRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001128228.3

BP6

Variant 9-137192572-TTCC-T is Benign according to our data. Variant chr9-137192572-TTCC-T is described in ClinVar as Benign. ClinVar VariationId is 165579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3 link	c.1842_1844delGGA	p.Glu615del	disruptive_inframe_deletion	Exon 2 of 4	ENST00000409012.6	NP_001121700.2	Q4KMQ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TPRN	ENST00000409012.6 link	c.1842_1844delGGA	p.Glu615del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001128228.3	ENSP00000387100.4	Q4KMQ1-1
TPRN	ENST00000477345.1 link	n.2563_2565delGGA		non_coding_transcript_exon_variant	Exon 1 of 3	1
TPRN	ENST00000333046.8 link	c.1236_1238delGGA	p.Glu413del	disruptive_inframe_deletion	Exon 2 of 3	2		ENSP00000327617.4	H3BLU1
TPRN	ENST00000541945.1 link	n.77_79delGGA		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00578

AC:

873

AN:

151102

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00610

AC:

1280

AN:

209928

AF XY:

0.00600

show subpopulations

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 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.:

AF XY:

0.00215

AC XY:

1507

AN XY:

701808

show subpopulations

African (AFR)

AF:

0.0191

AC:

615

AN:

32244

American (AMR)

AF:

0.00347

AC:

147

AN:

42356

Ashkenazi Jewish (ASJ)

AF:

0.000399

AC:

AN:

25050

East Asian (EAS)

AF:

0.00149

AC:

AN:

37572

South Asian (SAS)

AF:

0.00631

AC:

519

AN:

82270

European-Finnish (FIN)

AF:

0.00227

AC:

115

AN:

50560

Middle Eastern (MID)

AF:

0.00587

AC:

AN:

5620

European-Non Finnish (NFE)

AF:

0.00108

AC:

1164

AN:

1079768

Other (OTH)

AF:

0.00298

AC:

173

AN:

58068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

144

287

431

574

718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00577

AC:

873

AN:

151212

Hom.:

Cov.:

AF XY:

0.00571

AC XY:

422

AN XY:

73880

show subpopulations

African (AFR)

AF:

0.0173

AC:

714

AN:

41244

American (AMR)

AF:

0.00257

AC:

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00158

AC:

AN:

5064

South Asian (SAS)

AF:

0.00522

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.0000958

AC:

AN:

10440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00117

AC:

AN:

67736

Other (OTH)

AF:

0.00334

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

118

158

197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00774

Hom.:

Bravo

AF:

0.00701

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 15, 2019

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Sep 11, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over