9-137192293-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128228.3(TPRN):​c.2039C>T​(p.Pro680Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P680P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TPRN
NM_001128228.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.35
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09043124).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TPRNNM_001128228.3 linkuse as main transcriptc.2039C>T p.Pro680Leu missense_variant 3/4 ENST00000409012.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TPRNENST00000409012.6 linkuse as main transcriptc.2039C>T p.Pro680Leu missense_variant 3/41 NM_001128228.3 P1Q4KMQ1-1
TPRNENST00000477345.1 linkuse as main transcriptn.2760C>T non_coding_transcript_exon_variant 2/31
TPRNENST00000333046.8 linkuse as main transcriptc.1433C>T p.Pro478Leu missense_variant 3/32

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000315
AC:
46
AN:
1460652
Hom.:
0
Cov.:
31
AF XY:
0.0000275
AC XY:
20
AN XY:
726652
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000405
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152176
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2021The c.2039C>T (p.P680L) alteration is located in exon 3 (coding exon 3) of the TPRN gene. This alteration results from a C to T substitution at nucleotide position 2039, causing the proline (P) at amino acid position 680 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.072
.;T
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.11
N
LIST_S2
Benign
0.51
T;T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.090
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
.;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-2.5
D;D
REVEL
Benign
0.026
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.030
D;D
Polyphen
0.17
.;B
Vest4
0.32
MVP
0.030
ClinPred
0.23
T
GERP RS
-1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.059
gMVP
0.23

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.

Other links and lift over

dbSNP: rs369251781; hg19: chr9-140086745; API