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

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting

The ENST00000409012.6(TPRN):c.1844_1845insGGAGGAGGA(p.Glu619_Glu621dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 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 0.000073 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

TPRN
ENST00000409012.6 inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.164

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000727 (11/151270) while in subpopulation EAS AF= 0.00217 (11/5068). AF 95% confidence interval is 0.00122. There are 0 homozygotes in gnomad4. There are 5 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRN	NM_001128228.3 linkuse as main transcript	c.1844_1845insGGAGGAGGA	p.Glu619_Glu621dup	inframe_insertion	2/4	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6 linkuse as main transcript	c.1844_1845insGGAGGAGGA	p.Glu619_Glu621dup	inframe_insertion	2/4	1	NM_001128228.3	ENSP00000387100	P1	Q4KMQ1-1
TPRN	ENST00000477345.1 linkuse as main transcript	n.2565_2566insGGAGGAGGA		non_coding_transcript_exon_variant	1/3	1
TPRN	ENST00000333046.8 linkuse as main transcript	c.1238_1239insGGAGGAGGA	p.Glu417_Glu419dup	inframe_insertion	2/3	2		ENSP00000327617

Frequencies

GnomAD3 genomes

AF:

0.0000728

AC:

AN:

151158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00217

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

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1457156

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

724716

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000607

Gnomad4 SAS exome

AF:

0.0000582

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.0000830

GnomAD4 genome

AF:

0.0000727

AC:

AN:

151270

Hom.:

Cov.:

AF XY:

0.0000677

AC XY:

AN XY:

73908

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00217

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In-frame insertion of 3 amino acids in a repetitive region with no known function; Has not been previously published as pathogenic or benign to our knowledge -

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