NM_001128228.3:c.1845_1847delAGA

Variant names:

• chr9-137192569-CTCT-C
• rs727503521
• NM_001128228.3:c.1845_1847delAGA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001128228.3(TPRN):​c.1845_1847delAGA​(p.Glu616del) variant causes a disruptive 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 NM_001128228.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.23
• Publications: 0 publications found

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]

TPRN Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 79

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 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 CliVar 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 CliVar 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 CliVar 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 CliVar as Benign. Clinvar id is 165578.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.1845_1847delAGA	p.Glu616del	disruptive_inframe_deletion	Exon 2 of 4	ENST00000409012.6	NP_001121700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPRN	ENST00000409012.6	c.1845_1847delAGA	p.Glu616del	disruptive_inframe_deletion	Exon 2 of 4	1	NM_001128228.3	ENSP00000387100.4
TPRN	ENST00000477345.1	n.2566_2568delAGA		non_coding_transcript_exon_variant	Exon 1 of 3	1
TPRN	ENST00000333046.8	c.1239_1241delAGA	p.Glu414del	disruptive_inframe_deletion	Exon 2 of 3	2		ENSP00000327617.4
TPRN	ENST00000541945.1	n.*80_*82delAGA		downstream_gene_variant		4

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

Jun 03, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

dbSNP: rs727503521; hg19: chr9-140087021;