dbSNP rs28417902: TPRN:n.960C>T (chr9-137194178-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000477345.1(TPRN):n.960C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 152,378 control chromosomes in the GnomAD database, including 2,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.097 ( 2038 hom., cov: 33)

Exomes 𝑓: 0.024 ( 0 hom. )

Consequence

TPRN
ENST00000477345.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.51

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3 link	c.1726-1487C>T		intron_variant	Intron 1 of 3	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TPRN	ENST00000477345.1 link	n.960C>T	non_coding_transcript_exon_variant	Exon 1 of 3	1
TPRN	ENST00000409012.6 link	c.1726-1487C>T	intron_variant	Intron 1 of 3	1	NM_001128228.3	ENSP00000387100.4
TPRN	ENST00000333046.8 link	c.1120-1487C>T	intron_variant	Intron 1 of 2	2		ENSP00000327617.4
TPRN	ENST00000541945.1 link	n.91-1487C>T	intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes

AF:

0.0972

AC:

14780

AN:

152094

Hom.:

2036

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0369

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.0616

GnomAD4 exome

AF:

0.0241

AC:

AN:

166

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

AN XY:

124

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

126

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0973

AC:

14808

AN:

152212

Hom.:

2038

Cov.:

AF XY:

0.0969

AC XY:

7211

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.304

AC:

12633

AN:

41500

American (AMR)

AF:

0.0367

AC:

562

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.105

AC:

545

AN:

5180

South Asian (SAS)

AF:

0.149

AC:

715

AN:

4814

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00297

AC:

202

AN:

68010

Other (OTH)

AF:

0.0610

AC:

129

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

540

1080

1620

2160

2700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<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:

0.0346

Hom.:

664

Bravo

AF:

0.106

Asia WGS

AF:

0.160

AC:

557

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.0050

(source)

DANN

Benign

0.40

PhyloP100

-3.5

Mutation Taster

=100/0

polymorphism (auto)

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over