rs139459217

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001128228.3(TPRN):c.1748A>G(p.Lys583Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00298 in 1,613,868 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 8 hom. )

Consequence

TPRN
NM_001128228.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.15

Publications

6 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006991297).

BP6

Variant 9-137192669-T-C is Benign according to our data. Variant chr9-137192669-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 43960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00236 (359/152336) while in subpopulation NFE AF = 0.00341 (232/68028). AF 95% confidence interval is 0.00305. There are 0 homozygotes in GnomAd4. There are 174 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128228.3. 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
	TPRN	NM_001128228.3	MANE Select	c.1748A>G	p.Lys583Arg	missense	Exon 2 of 4	NP_001121700.2	Q4KMQ1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TPRN	ENST00000409012.6	TSL:1 MANE Select	c.1748A>G	p.Lys583Arg	missense	Exon 2 of 4	ENSP00000387100.4	Q4KMQ1-1
TPRN	ENST00000477345.1	TSL:1	n.2469A>G		non_coding_transcript_exon	Exon 1 of 3
TPRN	ENST00000961754.1		c.1682A>G	p.Lys561Arg	missense	Exon 2 of 4	ENSP00000631813.1

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00640

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00341

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00315

AC:

782

AN:

248394

AF XY:

0.00312

show subpopulations

Gnomad AFR exome

AF:

0.000555

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.00415

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00304

AC:

4446

AN:

1461532

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

2166

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.000388

AC:

AN:

33480

American (AMR)

AF:

0.000626

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00161

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00121

AC:

104

AN:

86258

European-Finnish (FIN)

AF:

0.00944

AC:

502

AN:

53152

Middle Eastern (MID)

AF:

0.000693

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00321

AC:

3573

AN:

1111936

Other (OTH)

AF:

0.00298

AC:

180

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

264

529

793

1058

1322

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.00236

AC:

359

AN:

152336

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

174

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41578

American (AMR)

AF:

0.00118

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000621

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00640

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00341

AC:

232

AN:

68028

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

107

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:

0.00306

Hom.:

Bravo

AF:

0.00201

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.00332

AC:

403

EpiCase

AF:

0.00300

EpiControl

AF:

0.00243

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

TPRN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.18

M_CAP

Benign

0.012

MetaRNN

Benign

0.0070

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.6

PhyloP100

4.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.94

REVEL

Benign

0.12

Sift

Uncertain

0.0080

Sift4G

Benign

0.15

Polyphen

0.82

Vest4

0.41

MVP

0.055

ClinPred

0.030

GERP RS

5.2

Varity_R

0.052

gMVP

0.19

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over