rs368771637

Positions:

• chr9-137192249-C-A
• chr9-137192249-C-G
• chr9-137192249-C-T

Variant summary

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

The ENST00000409012.6(TPRN):​c.2073+10G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPRN ENST00000409012.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

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=0.06939736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.2073+10G>T		intron_variant		ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6	c.2073+10G>T		intron_variant		1	NM_001128228.3	ENSP00000387100	P1
TPRN	ENST00000477345.1	n.2794+10G>T		intron_variant, non_coding_transcript_variant		1
TPRN	ENST00000333046.8	c.1477G>T	p.Gly493Trp	missense_variant	3/3	2		ENSP00000327617

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	0.16
DANN	Benign	0.96
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.97	T
MutationTaster	Benign	1.0	N;N
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.023
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
MutPred		0.44		Loss of loop (P = 0.0128);
MVP		0.030
ClinPred		0.085	T
GERP RS		1.2
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

Other links and lift over

dbSNP: rs368771637; hg19: chr9-140086701; COSMIC: COSV58809242; COSMIC: COSV58809242;