9-137194178-G-A

Position:

• chr9-137194178-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001128228.3(TPRN):​c.1726-1487C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0972 in 152,378 control chromosomes in the GnomAD database, including 2,038 homozygotes. 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: 𝑓 0.097 (2038 hom., cov: 33)
  • Exomes 𝑓: 0.024 (0 hom.)
• Consequence: TPRN NM_001128228.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.51

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPRN	NM_001128228.3	c.1726-1487C>T		intron_variant		ENST00000409012.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPRN	ENST00000409012.6	c.1726-1487C>T		intron_variant		1	NM_001128228.3	P1
TPRN	ENST00000477345.1	n.960C>T		non_coding_transcript_exon_variant	1/3	1
TPRN	ENST00000333046.8	c.1120-1487C>T		intron_variant		2
TPRN	ENST00000541945.1	n.91-1487C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14780 AN: 152094 Hom.: 2036 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00297

Gnomad OTH AF: 0.0616

GnomAD4 exome AF: 0.0241 AC: 4 AN: 166 Hom.: 0 Cov.: 0 AF XY: 0.0161 AC XY: 2 AN XY: 124

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0973 AC: 14808 AN: 152212 Hom.: 2038 Cov.: 33 AF XY: 0.0969 AC XY: 7211 AN XY: 74434

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.000659

Gnomad4 NFE AF: 0.00297

Gnomad4 OTH AF: 0.0610

Alfa AF: 0.0217 Hom.: 318

Bravo AF: 0.106

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.40

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: rs28417902; hg19: chr9-140088630;