NM_001042517.2:c.*219_*226dupTTTTTTTT

Variant names:

• chr13-59666357-C-CAAAAAAAA
• rs11421911
• NM_001042517.2:c.*219_*226dupTTTTTTTT

Variant summary

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

The NM_001042517.2(DIAPH3):​c.*219_*226dupTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000018 (0 hom., cov: 0)
• Consequence: DIAPH3 NM_001042517.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.612
• Publications: 0 publications found

Genes affected

DIAPH3 (HGNC:15480): (diaphanous related formin 3) This gene encodes a member of the diaphanous subfamily of the formin family. Members of this family are involved in actin remodeling and regulate cell movement and adhesion. Mutations in this gene are associated with autosomal dominant auditory neuropathy 1. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

DIAPH3 Gene-Disease associations (from GenCC):

• autosomal dominant auditory neuropathy 1

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• auditory neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.*219_*226dupTTTTTTTT		3_prime_UTR_variant	Exon 28 of 28	ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.*219_*226dupTTTTTTTT		3_prime_UTR_variant	Exon 28 of 28	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.*219_*226dupTTTTTTTT		downstream_gene_variant		1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.0000179 AC: 2 AN: 111942 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000363

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000179 AC: 2 AN: 111924 Hom.: 0 Cov.: 0 AF XY: 0.0000190 AC XY: 1 AN XY: 52670

African (AFR) AF: 0.00 AC: 0 AN: 29040

American (AMR) AF: 0.00 AC: 0 AN: 10806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2868

East Asian (EAS) AF: 0.00 AC: 0 AN: 3668

South Asian (SAS) AF: 0.00 AC: 0 AN: 3336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.0000363 AC: 2 AN: 55108

Other (OTH) AF: 0.00 AC: 0 AN: 1506

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.61

Splicing

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

Other links and lift over

dbSNP: rs11421911; hg19: chr13-60240491;