rs727503521

Positions:

• chr9-137192569-CTCT-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000409012.6(TPRN):​c.1845_1847del​(p.Glu621del) variant causes a inframe deletion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPRN ENST00000409012.6 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.23

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
• BP6: Variant 9-137192569-CTCT-C is Benign according to our data. Variant chr9-137192569-CTCT-C is described in ClinVar as [Benign]. Clinvar id is 165578.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-137192569-CTCT-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.1845_1847del	p.Glu621del	inframe_deletion	2/4	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6	c.1845_1847del	p.Glu621del	inframe_deletion	2/4	1	NM_001128228.3	ENSP00000387100	P1
TPRN	ENST00000477345.1	n.2566_2568del		non_coding_transcript_exon_variant	1/3	1
TPRN	ENST00000333046.8	c.1239_1241del	p.Glu419del	inframe_deletion	2/3	2		ENSP00000327617

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Jun 03, 2014

Glu621del in exon 2 of TPRN: This variant is not expected to have clinical signi ficance because it has been identified in 5.7% (455/8007) of European American c hromosomes and 6.5% (268/4126) of African American chromosomes by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS). -

Computational scores

Source: dbNSFP v4.3

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: rs727503521; hg19: chr9-140087021;