rs387906221

Variant names:

• chr9-137200476-AGCCGCGCCCCCGCCGCGCCCCC-A
• NM_001128228.3:c.214_235delGGGGGCGCGGCGGGGGCGCGGC

Your query was ambiguous. Multiple possible variants found:

• chr9-137200476-AGCCGCGCCCCCGCCGCGCCCCC-A
• chr9-137200476-AGCCGCGCCCCCGCCGCGCCCCC-AGCCGCGCCCCC
• chr9-137200476-AGCCGCGCCCCCGCCGCGCCCCC-AGCCGCGCCCCCGCCGCGCCCCCGCCGCGCCCCC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001128228.3(TPRN):​c.214_235delGGGGGCGCGGCGGGGGCGCGGC​(p.Gly72CysfsTer371) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 973,066 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: TPRN NM_001128228.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33

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 Pathogenic. Variant got 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPRN	NM_001128228.3	c.214_235delGGGGGCGCGGCGGGGGCGCGGC	p.Gly72CysfsTer371	frameshift_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.214_235delGGGGGCGCGGCGGGGGCGCGGC	p.Gly72CysfsTer371	frameshift_variant	Exon 1 of 4	1	NM_001128228.3	ENSP00000387100.4
TPRN	ENST00000541945.1	n.90+3606_90+3627delGGGGGCGCGGCGGGGGCGCGGC		intron_variant	Intron 1 of 1	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000411 AC: 4 AN: 973066 Hom.: 0 AF XY: 0.00000427 AC XY: 2 AN XY: 468160

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: 0.000176

Gnomad4 NFE exome AF: 0.00000117

Gnomad4 OTH exome AF: 0.0000288

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr9-140094928;