chr9-137192133-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001128228.3(TPRN):​c.2115C>A​(p.Ser705Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

TPRN
NM_001128228.3 missense

Scores

4
5
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.964
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]

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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.30013043).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TPRNNM_001128228.3 linkc.2115C>A p.Ser705Arg missense_variant Exon 4 of 4 ENST00000409012.6 NP_001121700.2 Q4KMQ1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TPRNENST00000409012.6 linkc.2115C>A p.Ser705Arg missense_variant Exon 4 of 4 1 NM_001128228.3 ENSP00000387100.4 Q4KMQ1-1
TPRNENST00000477345.1 linkn.2836C>A non_coding_transcript_exon_variant Exon 3 of 3 1
TPRNENST00000333046.8 linkc.1593C>A p.Ser531Arg missense_variant Exon 3 of 3 2 ENSP00000327617.4 H3BLU1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461202
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726930
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Pathogenic
0.34
D
BayesDel_noAF
Pathogenic
0.24
CADD
Benign
7.0
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.52
T;D
M_CAP
Benign
0.069
D
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-2.1
N;N
REVEL
Uncertain
0.33
Sift
Pathogenic
0.0
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
1.0
.;D
Vest4
0.86
MutPred
0.098
.;Loss of phosphorylation at S705 (P = 0.0182);
MVP
0.014
ClinPred
0.97
D
GERP RS
-5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.59
gMVP
0.62

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs372125769; hg19: chr9-140086585; API