13-59666695-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001042517.2(DIAPH3):c.3471G>A(p.Ala1157Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0518 in 1,614,044 control chromosomes in the GnomAD database, including 2,270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 213 hom., cov: 33)

Exomes 𝑓: 0.052 ( 2057 hom. )

Consequence

DIAPH3
NM_001042517.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.15

Publications

6 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 13-59666695-C-T is Benign according to our data. Variant chr13-59666695-C-T is described in ClinVar as [Benign]. Clinvar id is 517828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.15 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2 link	c.3471G>A	p.Ala1157Ala	synonymous_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.3471G>A	p.Ala1157Ala	synonymous_variant	Exon 28 of 28	1	NM_001042517.2	ENSP00000383178.3		Q9NSV4-3
DIAPH3	ENST00000400319.5 link	c.3261G>A	p.Ala1087Ala	synonymous_variant	Exon 26 of 26	1		ENSP00000383173.1		Q9NSV4-6

Frequencies

GnomAD3 genomes

AF:

0.0507

AC:

7716

AN:

152102

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.0304

Gnomad ASJ

AF:

0.0822

Gnomad EAS

AF:

0.0333

Gnomad SAS

AF:

0.0430

Gnomad FIN

AF:

0.0637

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0513

Gnomad OTH

AF:

0.0464

GnomAD2 exomes

AF:

0.0471

AC:

11750

AN:

249440

AF XY:

0.0472

show subpopulations

Gnomad AFR exome

AF:

0.0526

Gnomad AMR exome

AF:

0.0189

Gnomad ASJ exome

AF:

0.0798

Gnomad EAS exome

AF:

0.0439

Gnomad FIN exome

AF:

0.0660

Gnomad NFE exome

AF:

0.0509

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0520

AC:

75969

AN:

1461824

Hom.:

2057

Cov.:

AF XY:

0.0518

AC XY:

37635

AN XY:

727208

show subpopulations

African (AFR)

AF:

0.0533

AC:

1785

AN:

33480

American (AMR)

AF:

0.0194

AC:

869

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0763

AC:

1993

AN:

26130

East Asian (EAS)

AF:

0.0462

AC:

1832

AN:

39688

South Asian (SAS)

AF:

0.0403

AC:

3477

AN:

86254

European-Finnish (FIN)

AF:

0.0648

AC:

3459

AN:

53416

Middle Eastern (MID)

AF:

0.0298

AC:

172

AN:

5768

European-Non Finnish (NFE)

AF:

0.0533

AC:

59310

AN:

1111970

Other (OTH)

AF:

0.0509

AC:

3072

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

4497

8993

13490

17986

22483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0507

AC:

7713

AN:

152220

Hom.:

213

Cov.:

AF XY:

0.0499

AC XY:

3715

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0546

AC:

2268

AN:

41538

American (AMR)

AF:

0.0302

AC:

462

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0822

AC:

285

AN:

3466

East Asian (EAS)

AF:

0.0332

AC:

172

AN:

5178

South Asian (SAS)

AF:

0.0429

AC:

207

AN:

4828

European-Finnish (FIN)

AF:

0.0637

AC:

674

AN:

10586

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0513

AC:

3489

AN:

68012

Other (OTH)

AF:

0.0455

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

378

756

1133

1511

1889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0529

Hom.:

101

Bravo

AF:

0.0486

Asia WGS

AF:

0.0380

AC:

131

AN:

3478

EpiCase

AF:

0.0485

EpiControl

AF:

0.0497

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 26, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

1.1

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

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13-59666695-C-T

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