Genetic Variant DIAPH3:c.*226dupT (chr13-59666357-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001042517.2(DIAPH3):c.*226dupT 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 0.59 ( 17401 hom., cov: 0)

Exomes 𝑓: 0.24 ( 39 hom. )

Consequence

DIAPH3
NM_001042517.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.612

Publications

0 publications found

Variant links:

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

DIAPH3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2 link	c.*226dupT		3_prime_UTR_variant	Exon 28 of 28	ENST00000400324.9	NP_001035982.1	Q9NSV4-3B4DPV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9 link	c.*226dupT		3_prime_UTR_variant	Exon 28 of 28	1	NM_001042517.2	ENSP00000383178.3		Q9NSV4-3
DIAPH3	ENST00000400319.5 link	c.*226dupT		downstream_gene_variant		1		ENSP00000383173.1		Q9NSV4-6

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

66325

AN:

111846

Hom.:

17407

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.610

Gnomad ASJ

AF:

0.603

Gnomad EAS

AF:

0.541

Gnomad SAS

AF:

0.570

Gnomad FIN

AF:

0.671

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.555

GnomAD4 exome

AF:

0.241

AC:

45553

AN:

189138

Hom.:

Cov.:

AF XY:

0.239

AC XY:

23822

AN XY:

99600

show subpopulations

African (AFR)

AF:

0.206

AC:

949

AN:

4600

American (AMR)

AF:

0.240

AC:

1580

AN:

6580

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

1432

AN:

5982

East Asian (EAS)

AF:

0.203

AC:

2265

AN:

11142

South Asian (SAS)

AF:

0.222

AC:

3897

AN:

17586

European-Finnish (FIN)

AF:

0.271

AC:

2411

AN:

8910

Middle Eastern (MID)

AF:

0.201

AC:

183

AN:

912

European-Non Finnish (NFE)

AF:

0.247

AC:

30211

AN:

122202

Other (OTH)

AF:

0.234

AC:

2625

AN:

11224

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.416

Heterozygous variant carriers

1632

3263

4895

6526

8158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.593

AC:

66307

AN:

111830

Hom.:

17401

Cov.:

AF XY:

0.591

AC XY:

31124

AN XY:

52622

show subpopulations

African (AFR)

AF:

0.486

AC:

14108

AN:

29010

American (AMR)

AF:

0.610

AC:

6575

AN:

10786

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

1728

AN:

2868

East Asian (EAS)

AF:

0.542

AC:

1986

AN:

3664

South Asian (SAS)

AF:

0.571

AC:

1897

AN:

3324

European-Finnish (FIN)

AF:

0.671

AC:

3060

AN:

4560

Middle Eastern (MID)

AF:

0.564

AC:

115

AN:

204

European-Non Finnish (NFE)

AF:

0.642

AC:

35383

AN:

55084

Other (OTH)

AF:

0.553

AC:

831

AN:

1504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1411

2823

4234

5646

7057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 08, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-59666357-C-CA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over