13-60016173-C-T

Position:

• chr13-60016173-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001042517.2(DIAPH3):​c.627-28G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,602,014 control chromosomes in the GnomAD database, including 71,942 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5371 hom., cov: 33)
  • Exomes 𝑓: 0.29 (66571 hom.)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.913

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 13-60016173-C-T is Benign according to our data. Variant chr13-60016173-C-T is described in ClinVar as [Benign]. Clinvar id is 1272224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.627-28G>A		intron_variant		ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.627-28G>A		intron_variant		1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.417-28G>A		intron_variant		1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36466 AN: 151994 Hom.: 5362 Cov.: 33

Gnomad AFR AF: 0.0908

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.273 AC: 66472 AN: 243246 Hom.: 10601 AF XY: 0.272 AC XY: 35879 AN XY: 132042

Gnomad AFR exome AF: 0.0853

Gnomad AMR exome AF: 0.440

Gnomad ASJ exome AF: 0.261

Gnomad EAS exome AF: 0.00130

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.306

Gnomad NFE exome AF: 0.303

Gnomad OTH exome AF: 0.274

GnomAD4 exome AF: 0.294 AC: 426470 AN: 1449902 Hom.: 66571 Cov.: 28 AF XY: 0.292 AC XY: 211012 AN XY: 721992

Gnomad4 AFR exome AF: 0.0842

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.00142

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.314

Gnomad4 OTH exome AF: 0.272

GnomAD4 genome AF: 0.240 AC: 36483 AN: 152112 Hom.: 5371 Cov.: 33 AF XY: 0.240 AC XY: 17833 AN XY: 74330

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.249

Alfa AF: 0.262 Hom.: 1193

Bravo AF: 0.241

Asia WGS AF: 0.104 AC: 363 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.45
DANN	Benign	0.61

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: rs12429010; hg19: chr13-60590307;