9-137192161-C-T

Variant names:

• chr9-137192161-C-T
• NM_001128228.3:c.2087G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128228.3(TPRN):​c.2087G>A​(p.Ser696Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPRN NM_001128228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50

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]

ACMG classification

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=0.13147193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.2087G>A	p.Ser696Asn	missense_variant	Exon 4 of 4	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6	c.2087G>A	p.Ser696Asn	missense_variant	Exon 4 of 4	1	NM_001128228.3	ENSP00000387100.4
TPRN	ENST00000477345.1	n.2808G>A		non_coding_transcript_exon_variant	Exon 3 of 3	1
TPRN	ENST00000333046.8	c.1565G>A	p.Ser522Asn	missense_variant	Exon 3 of 3	2		ENSP00000327617.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Jan 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 696 of the TPRN protein (p.Ser696Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with TPRN-related conditions. Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TPRN protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0059	.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.21
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	.;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.047
Sift	Benign	0.10	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.90	.;P
Vest4		0.059
MutPred		0.14		.;Loss of phosphorylation at S696 (P = 0.0403);
MVP		0.048
ClinPred		0.39	T
GERP RS		4.8
Varity_R		0.079
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140086613;