13-59666437-A-T

Position:

• chr13-59666437-A-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.*147T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 926,022 control chromosomes in the GnomAD database, including 217,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (33986 hom., cov: 28)
  • Exomes 𝑓: 0.69 (183366 hom.)
• Consequence: DIAPH3 NM_001042517.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.471

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 13-59666437-A-T is Benign according to our data. Variant chr13-59666437-A-T is described in ClinVar as [Benign]. Clinvar id is 1239594.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-59666437-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.*147T>A		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.*147T>A		3_prime_UTR_variant	28/28	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000649952.1	n.593T>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 100812 AN: 150766 Hom.: 33968 Cov.: 28

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.686

Gnomad OTH AF: 0.652

GnomAD4 exome AF: 0.685 AC: 531336 AN: 775144 Hom.: 183366 Cov.: 10 AF XY: 0.685 AC XY: 269968 AN XY: 394144

Gnomad4 AFR exome AF: 0.600

Gnomad4 AMR exome AF: 0.654

Gnomad4 ASJ exome AF: 0.717

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.644

Gnomad4 FIN exome AF: 0.782

Gnomad4 NFE exome AF: 0.684

Gnomad4 OTH exome AF: 0.676

GnomAD4 genome AF: 0.669 AC: 100867 AN: 150878 Hom.: 33986 Cov.: 28 AF XY: 0.673 AC XY: 49558 AN XY: 73594

Gnomad4 AFR AF: 0.603

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.737

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.794

Gnomad4 NFE AF: 0.686

Gnomad4 OTH AF: 0.649

Alfa AF: 0.685 Hom.: 4450

Bravo AF: 0.656

Asia WGS AF: 0.681 AC: 2359 AN: 3462

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	Mar 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.0
DANN	Benign	0.64

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: rs3803205; hg19: chr13-60240571;