rs267607135

Variant names:

• chr9-137199473-C-A
• NM_001128228.3:c.1239G>T

Your query was ambiguous. Multiple possible variants found:

• chr9-137199473-C-A
• chr9-137199473-C-T

Variant summary

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

The NM_001128228.3(TPRN):​c.1239G>T​(p.Trp413Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict 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: 6.9e-7 (0 hom.)
• Consequence: TPRN NM_001128228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03

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=0.15371478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.1239G>T	p.Trp413Cys	missense_variant	Exon 1 of 4	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6	c.1239G>T	p.Trp413Cys	missense_variant	Exon 1 of 4	1	NM_001128228.3	ENSP00000387100.4
TPRN	ENST00000333046.8	c.633G>T	p.Trp211Cys	missense_variant	Exon 1 of 3	2		ENSP00000327617.4
TPRN	ENST00000541945.1	n.90+4631G>T		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446038 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 718258

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: 0.0000199

Gnomad4 NFE exome AF: 0.00

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.0050	.;T
Eigen	Benign	0.030
Eigen_PC	Benign	-0.053
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	.;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.086
Sift	Benign	0.031	D;D
Sift4G	Benign	0.11	T;T
Polyphen		0.98	.;D
Vest4		0.26
MutPred		0.24		.;Loss of MoRF binding (P = 0.0205);
MVP		0.095
ClinPred		0.44	T
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.12
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140093925;