Variant 9-137192237-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1

The NM_001128228.3(TPRN):c.2073+22C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,613,150 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00028 ( 9 hom. )

Consequence

TPRN
NM_001128228.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.69

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040705204).

BP6

Variant 9-137192237-G-A is Benign according to our data. Variant chr9-137192237-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1199132.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000144 (22/152294) while in subpopulation SAS AF= 0.00456 (22/4826). AF 95% confidence interval is 0.00309. There are 1 homozygotes in gnomad4. There are 16 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPRN	NM_001128228.3 linkuse as main transcript	c.2073+22C>T		intron_variant		ENST00000409012.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPRN	ENST00000409012.6 linkuse as main transcript	c.2073+22C>T		intron_variant		1	NM_001128228.3	P1	Q4KMQ1-1
TPRN	ENST00000477345.1 linkuse as main transcript	n.2794+22C>T		intron_variant, non_coding_transcript_variant		1
TPRN	ENST00000333046.8 linkuse as main transcript	c.1489C>T	p.Arg497Cys	missense_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152176

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:

0.00

Gnomad SAS

AF:

0.00455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000547

AC:

137

AN:

250514

Hom.:

AF XY:

0.000766

AC XY:

104

AN XY:

135736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000279

AC:

408

AN:

1460856

Hom.:

Cov.:

AF XY:

0.000407

AC XY:

296

AN XY:

726744

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00441

Gnomad4 FIN exome

AF:

0.0000572

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000144

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000521

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000585

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

Cadd

Benign

0.054

Dann

Benign

0.97

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.44

M_CAP

Benign

0.00021

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-0.040

REVEL

Benign

0.013

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.013

MutPred

0.42

Gain of catalytic residue at S501 (P = 0.041);

MVP

0.030

ClinPred

0.027

GERP RS

-4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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