chr9-137192572-TTCCTCC-T

Variant names:

• chr9-137192572-TTCCTCC-T
• rs376810326
• NM_001128228.3:c.1839_1844delGGAGGA

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP3 BP6_Very_Strong BS1

The NM_001128228.3(TPRN):​c.1839_1844delGGAGGA​(p.Glu614_Glu615del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000663 in 1,608,372 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. E613E) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00056 (1 hom.)
• Consequence: TPRN NM_001128228.3 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.06
• Publications: 3 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: Benign. The variant received -13 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001128228.3
• BP6: Variant 9-137192572-TTCCTCC-T is Benign according to our data. Variant chr9-137192572-TTCCTCC-T is described in ClinVar as Benign. ClinVar VariationId is 179337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00165 (250/151268) while in subpopulation EAS AF = 0.0101 (51/5068). AF 95% confidence interval is 0.00786. There are 1 homozygotes in GnomAd4. There are 132 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.1839_1844delGGAGGA	p.Glu614_Glu615del	disruptive_inframe_deletion	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.1839_1844delGGAGGA	p.Glu614_Glu615del	disruptive_inframe_deletion	Exon 2 of 4	ENSP00000387100.4	Q4KMQ1-1
	TPRN	ENST00000477345.1	TSL:1	n.2560_2565delGGAGGA		non_coding_transcript_exon	Exon 1 of 3
	TPRN	ENST00000961754.1		c.1773_1778delGGAGGA	p.Glu592_Glu593del	disruptive_inframe_deletion	Exon 2 of 4	ENSP00000631813.1

Frequencies

GnomAD3 genomes AF: 0.00165 AC: 250 AN: 151156 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00224

Gnomad ASJ AF: 0.000868

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.00241

GnomAD2 exomes AF: 0.00188 AC: 395 AN: 209928 AF XY: 0.00165

Gnomad AFR exome AF: 0.00349

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.000554

Gnomad EAS exome AF: 0.0172

Gnomad FIN exome AF: 0.0000545

Gnomad NFE exome AF: 0.000217

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000561 AC: 817 AN: 1457104 Hom.: 1 AF XY: 0.000534 AC XY: 387 AN XY: 724688

African (AFR) AF: 0.00342 AC: 114 AN: 33352

American (AMR) AF: 0.00117 AC: 52 AN: 44342

Ashkenazi Jewish (ASJ) AF: 0.000422 AC: 11 AN: 26056

East Asian (EAS) AF: 0.00812 AC: 321 AN: 39550

South Asian (SAS) AF: 0.000338 AC: 29 AN: 85878

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52510

Middle Eastern (MID) AF: 0.000695 AC: 4 AN: 5754

European-Non Finnish (NFE) AF: 0.000210 AC: 233 AN: 1109458

Other (OTH) AF: 0.000880 AC: 53 AN: 60204

GnomAD4 genome AF: 0.00165 AC: 250 AN: 151268 Hom.: 1 Cov.: 33 AF XY: 0.00179 AC XY: 132 AN XY: 73908

African (AFR) AF: 0.00310 AC: 128 AN: 41254

American (AMR) AF: 0.00217 AC: 33 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.000868 AC: 3 AN: 3458

East Asian (EAS) AF: 0.0101 AC: 51 AN: 5068

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4788

European-Finnish (FIN) AF: 0.000191 AC: 2 AN: 10456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000339 AC: 23 AN: 67754

Other (OTH) AF: 0.00239 AC: 5 AN: 2096

Alfa AF: 0.000110 Hom.: 0

Bravo AF: 0.00219

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=170/30	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs376810326; hg19: chr9-140087024;