9-137192572-TTCCTCCTCCTCCTCCTCC-TTCCTCCTCCTCC

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3BP6_Very_StrongBS1

The NM_001128228.3(TPRN):c.1839_1844delGGAGGA(p.Glu614_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 0.000663 in 1,608,372 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E613E) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0017 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 1 hom. )

Consequence

TPRN
NM_001128228.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.06

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 -13 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001128228.3

BP6

Variant 9-137192572-TTCCTCC-T is Benign according to our data. Variant chr9-137192572-TTCCTCC-T is described in ClinVar as Benign. ClinVar VariationId is 179337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00165 (250/151268) while in subpopulation EAS AF = 0.0101 (51/5068). AF 95% confidence interval is 0.00786. There are 1 homozygotes in GnomAd4. There are 132 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3 link	c.1839_1844delGGAGGA	p.Glu614_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.1839_1844delGGAGGA	p.Glu614_Glu615del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001128228.3	ENSP00000387100.4	Q4KMQ1-1
TPRN	ENST00000477345.1 link	n.2560_2565delGGAGGA		non_coding_transcript_exon_variant	Exon 1 of 3	1
TPRN	ENST00000333046.8 link	c.1233_1238delGGAGGA	p.Glu412_Glu413del	disruptive_inframe_deletion	Exon 2 of 3	2		ENSP00000327617.4	H3BLU1
TPRN	ENST00000541945.1 link	n.74_79delGGAGGA		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00165

AC:

250

AN:

151156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00224

Gnomad ASJ

AF:

0.000868

Gnomad EAS

AF:

0.0100

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.00241

GnomAD2 exomes

AF:

0.00188

AC:

395

AN:

209928

AF XY:

0.00165

show subpopulations

Gnomad AFR exome

AF:

0.00349

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.000554

Gnomad EAS exome

AF:

0.0172

Gnomad FIN exome

AF:

0.0000545

Gnomad NFE exome

AF:

0.000217

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.000561

AC:

817

AN:

1457104

Hom.:

AF XY:

0.000534

AC XY:

387

AN XY:

724688

show subpopulations

African (AFR)

AF:

0.00342

AC:

114

AN:

33352

American (AMR)

AF:

0.00117

AC:

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.000422

AC:

AN:

26056

East Asian (EAS)

AF:

0.00812

AC:

321

AN:

39550

South Asian (SAS)

AF:

0.000338

AC:

AN:

85878

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52510

Middle Eastern (MID)

AF:

0.000695

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000210

AC:

233

AN:

1109458

Other (OTH)

AF:

0.000880

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.00165

AC:

250

AN:

151268

Hom.:

Cov.:

AF XY:

0.00179

AC XY:

132

AN XY:

73908

show subpopulations

African (AFR)

AF:

0.00310

AC:

128

AN:

41254

American (AMR)

AF:

0.00217

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.000868

AC:

AN:

3458

East Asian (EAS)

AF:

0.0101

AC:

AN:

5068

South Asian (SAS)

AF:

0.00104

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.000191

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000339

AC:

AN:

67754

Other (OTH)

AF:

0.00239

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000110

Hom.:

Bravo

AF:

0.00219

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 15, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 02, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Nov 05, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Glu620_Glu621del in Exon 2 of TPRN: This variant is not expected to have clinica l significance because it has been identified in 1.5% (114/7666) of European Ame rican chromosomes and 1.2% (46/3904) of African American chromosomes by the NHLB I Exome sequencing project (http://evs.gs.washington.edu/EVS/; dbSNP rs77086130) . -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.1

Mutation Taster

=170/30

polymorphism

(source)

Splicing

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