chr9-137192572-TTCC-T

Variant names:

• chr9-137192571-CTTC-CT
• NM_001128228.3:c.1843_1844delGA

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001128228.3(TPRN):​c.1843_1844delGA​(p.Glu615ArgfsTer39) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TPRN NM_001128228.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• 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: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128228.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRN	NM_001128228.3	MANE Select	c.1843_1844delGA	p.Glu615ArgfsTer39	frameshift	Exon 2 of 4	NP_001121700.2	Q4KMQ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPRN	ENST00000409012.6	TSL:1 MANE Select	c.1843_1844delGA	p.Glu615ArgfsTer39	frameshift	Exon 2 of 4	ENSP00000387100.4	Q4KMQ1-1
	TPRN	ENST00000477345.1	TSL:1	n.2564_2565delGA		non_coding_transcript_exon	Exon 1 of 3
	TPRN	ENST00000961754.1		c.1777_1778delGA	p.Glu593ArgfsTer39	frameshift	Exon 2 of 4	ENSP00000631813.1

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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr9-140087023;