9-137192572-TTCCTCCTCCTCCTCCTCC-TTCCTCCTCCTCCTCCTCCTCC

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_1844dupGGA(p.Glu615dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,608,350 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 5 hom. )

Consequence

TPRN
NM_001128228.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

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

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-T-TTCC is Benign according to our data. Variant chr9-137192572-T-TTCC is described in ClinVar as Benign. ClinVar VariationId is 43961.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 = 0.00225 (340/151268) while in subpopulation EAS AF = 0.0166 (84/5068). AF 95% confidence interval is 0.0137. There are 1 homozygotes in GnomAd4. There are 165 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3 link	c.1842_1844dupGGA	p.Glu615dup	disruptive_inframe_insertion	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_1844dupGGA	p.Glu615dup	disruptive_inframe_insertion	Exon 2 of 4	1	NM_001128228.3	ENSP00000387100.4	Q4KMQ1-1
TPRN	ENST00000477345.1 link	n.2563_2565dupGGA		non_coding_transcript_exon_variant	Exon 1 of 3	1
TPRN	ENST00000333046.8 link	c.1236_1238dupGGA	p.Glu413dup	disruptive_inframe_insertion	Exon 2 of 3	2		ENSP00000327617.4	H3BLU1
TPRN	ENST00000541945.1 link	n.77_79dupGGA		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00224

AC:

338

AN:

151156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00310

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0167

Gnomad SAS

AF:

0.00501

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000443

Gnomad OTH

AF:

0.00434

GnomAD2 exomes

AF:

0.00296

AC:

622

AN:

209928

AF XY:

0.00284

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.00152

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.0213

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000609

Gnomad OTH exome

AF:

0.00208

GnomAD4 exome

AF:

0.00125

AC:

1825

AN:

1457082

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

948

AN XY:

724676

show subpopulations

African (AFR)

AF:

0.00390

AC:

130

AN:

33352

American (AMR)

AF:

0.00151

AC:

AN:

44342

Ashkenazi Jewish (ASJ)

AF:

0.000230

AC:

AN:

26056

East Asian (EAS)

AF:

0.0170

AC:

673

AN:

39552

South Asian (SAS)

AF:

0.00483

AC:

415

AN:

85878

European-Finnish (FIN)

AF:

0.0000571

AC:

AN:

52522

Middle Eastern (MID)

AF:

0.00122

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.000343

AC:

380

AN:

1109424

Other (OTH)

AF:

0.00239

AC:

144

AN:

60202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

113

227

340

454

567

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00225

AC:

340

AN:

151268

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

165

AN XY:

73906

show subpopulations

African (AFR)

AF:

0.00349

AC:

144

AN:

41252

American (AMR)

AF:

0.00309

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.0166

AC:

AN:

5068

South Asian (SAS)

AF:

0.00501

AC:

AN:

4788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000443

AC:

AN:

67754

Other (OTH)

AF:

0.00525

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.000183

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 21, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 11, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 21, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Glu607[16] in exon 2 of TPRN: This duplication is unlikely to have clinical si gnificance because it is located within a repeat region of glutamate (Glu) resid ues and expansion of this repeat by one or more residues has been seen in at lea st 2.4% of East Asian chromosomes by the Exome Aggregation Consortium (ExAC; htt p://exac.broadinstitute.org). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Mutation Taster

=75/25

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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