13-59666357-C-CAAA

Position:

• chr13-59666357-C-CAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001042517.2(DIAPH3):​c.*224_*226dupTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (2 hom., cov: 0)
  • Exomes 𝑓: 0.00075 (0 hom.)
• Consequence: DIAPH3 NM_001042517.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.612

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 13-59666357-C-CAAA is Benign according to our data. Variant chr13-59666357-C-CAAA is described in ClinVar as [Likely_benign]. Clinvar id is 1178019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 332 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.*224_*226dupTTT		3_prime_UTR_variant	28/28	ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324	c.*224_*226dupTTT		3_prime_UTR_variant	28/28	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000649952.1	n.670_672dupTTT		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 334 AN: 111908 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000595

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000109

Gnomad OTH AF: 0.00201

GnomAD4 exome AF: 0.000747 AC: 142 AN: 190106 Hom.: 0 Cov.: 0 AF XY: 0.000729 AC XY: 73 AN XY: 100090

Gnomad4 AFR exome AF: 0.00346

Gnomad4 AMR exome AF: 0.000906

Gnomad4 ASJ exome AF: 0.00117

Gnomad4 EAS exome AF: 0.000715

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.000557

Gnomad4 NFE exome AF: 0.000586

Gnomad4 OTH exome AF: 0.000798

GnomAD4 genome AF: 0.00297 AC: 332 AN: 111890 Hom.: 2 Cov.: 0 AF XY: 0.00287 AC XY: 151 AN XY: 52662

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.00102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000600

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000109

Gnomad4 OTH AF: 0.00199

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11421911; hg19: chr13-60240491;