13-59666357-CAAAAAA-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr13-59666357-C-CAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
• rs11421911
• NM_001042517.2:c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Variant summary

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

The NM_001042517.2(DIAPH3):​c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000089 (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 nonsyndromic hearing loss

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

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autosomal dominant auditory neuropathy 1

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042517.2. 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
	DIAPH3	NM_001042517.2	MANE Select	c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		3_prime_UTR	Exon 28 of 28	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		3_prime_UTR	Exon 27 of 27	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		3_prime_UTR	Exon 26 of 26	NP_001245296.1	Q9NSV4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	ENST00000400324.9	TSL:1 MANE Select	c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		3_prime_UTR	Exon 28 of 28	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000649952.1		n.672_673insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		non_coding_transcript_exon	Exon 2 of 2
	DIAPH3	ENST00000377908.6	TSL:1	c.*226_*227insTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT		downstream_gene	N/A	ENSP00000367141.2	Q9NSV4-4

Frequencies

GnomAD3 genomes AF: 0.00000893 AC: 1 AN: 111942 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000345

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000893 AC: 1 AN: 111942 Hom.: 0 Cov.: 0 AF XY: 0.0000190 AC XY: 1 AN XY: 52656

African (AFR) AF: 0.0000345 AC: 1 AN: 29000

American (AMR) AF: 0.00 AC: 0 AN: 10802

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3686

South Asian (SAS) AF: 0.00 AC: 0 AN: 3360

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 226

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55120

Other (OTH) AF: 0.00 AC: 0 AN: 1494

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;