Variant 9-137192572-TTCCTCCTCCTCCTCCTCC-TTCC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001128228.3(TPRN):c.1830_1844delGGAGGAGGAGGAGGA(p.Glu611_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 0.0000528 in 1,608,426 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

TPRN
NM_001128228.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.63

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 links:

TPRN (HGNC:):

TPRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRN	NM_001128228.3 linkuse as main transcript	c.1830_1844delGGAGGAGGAGGAGGA	p.Glu611_Glu615del	disruptive_inframe_deletion	2/4	ENST00000409012.6	NP_001121700.2	Q4KMQ1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TPRN	ENST00000409012.6 linkuse as main transcript	c.1830_1844delGGAGGAGGAGGAGGA	p.Glu611_Glu615del	disruptive_inframe_deletion	2/4	1	NM_001128228.3	ENSP00000387100.4	Q4KMQ1-1
TPRN	ENST00000477345.1 linkuse as main transcript	n.2551_2565delGGAGGAGGAGGAGGA		non_coding_transcript_exon_variant	1/3	1
TPRN	ENST00000333046.8 linkuse as main transcript	c.1224_1238delGGAGGAGGAGGAGGA	p.Glu409_Glu413del	disruptive_inframe_deletion	2/3	2		ENSP00000327617.4	H3BLU1

Frequencies

GnomAD3 genomes

AF:

0.000198

AC:

AN:

151158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000583

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00118

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000162

AC:

AN:

209928

Hom.:

AF XY:

0.000141

AC XY:

AN XY:

113872

show subpopulations

Gnomad AFR exome

AF:

0.000668

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1457156

Hom.:

AF XY:

0.0000359

AC XY:

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.000809

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000405

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.000231

AC:

AN:

151270

Hom.:

Cov.:

AF XY:

0.000298

AC XY:

AN XY:

73908

show subpopulations

Gnomad4 AFR

AF:

0.000703

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00118

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 14, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 05, 2021	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with TPRN-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant, c.1830_1844del, results in the deletion of 5 amino acid(s) of the TPRN protein (p.Glu617_Glu621del), but otherwise preserves the integrity of the reading frame. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over