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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001128228.3(TPRN):c.1844_1845insGGA(p.Glu620dup) variant causes a 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 inframe_insertion

Scores

Not classified

Clinical Significance

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

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 Benign. Variant got -16 ACMG points.

BP6

Variant 9-137192572-T-TTCC is Benign according to our data. Variant chr9-137192572-T-TTCC is described in ClinVar as [Benign]. Clinvar id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRN	NM_001128228.3 linkuse as main transcript	c.1844_1845insGGA	p.Glu620dup	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_1845insGGA	p.Glu620dup	inframe_insertion	2/4	1	NM_001128228.3	ENSP00000387100	P1	Q4KMQ1-1
TPRN	ENST00000477345.1 linkuse as main transcript	n.2565_2566insGGA		non_coding_transcript_exon_variant	1/3	1
TPRN	ENST00000333046.8 linkuse as main transcript	c.1238_1239insGGA	p.Glu418dup	inframe_insertion	2/3	2		ENSP00000327617

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

GnomAD3 exomes

AF:

0.00296

AC:

622

AN:

209928

Hom.:

AF XY:

0.00284

AC XY:

323

AN XY:

113872

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 SAS exome

AF:

0.00514

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

Gnomad4 AFR exome

AF:

0.00390

Gnomad4 AMR exome

AF:

0.00151

Gnomad4 ASJ exome

AF:

0.000230

Gnomad4 EAS exome

AF:

0.0170

Gnomad4 SAS exome

AF:

0.00483

Gnomad4 FIN exome

AF:

0.0000571

Gnomad4 NFE exome

AF:

0.000343

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00225

AC:

340

AN:

151268

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

165

AN XY:

73906

show subpopulations

Gnomad4 AFR

AF:

0.00349

Gnomad4 AMR

AF:

0.00309

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0166

Gnomad4 SAS

AF:

0.00501

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000443

Gnomad4 OTH

AF:

0.00525

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2020	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jan 21, 2015

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

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