Variant chr13-59666695-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

DIAPH3 (HGNC:):

DIAPH3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr13-59666695-C-T is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2 linkuse as main transcript	c.3471G>A	p.Ala1157Ala	synonymous_variant	28/28	ENST00000400324.9	NP_001035982.1	Q9NSV4-3B4DPV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9 linkuse as main transcript	c.3471G>A	p.Ala1157Ala	synonymous_variant	28/28	1	NM_001042517.2	ENSP00000383178.3		Q9NSV4-3
DIAPH3	ENST00000400319.5 linkuse as main transcript	c.3261G>A	p.Ala1087Ala	synonymous_variant	26/26	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

GnomAD3 exomes

AF:

0.0471

AC:

11750

AN:

249440

Hom.:

311

AF XY:

0.0472

AC XY:

6387

AN XY:

135312

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 SAS exome

AF:

0.0404

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

Gnomad4 AFR exome

AF:

0.0533

Gnomad4 AMR exome

AF:

0.0194

Gnomad4 ASJ exome

AF:

0.0763

Gnomad4 EAS exome

AF:

0.0462

Gnomad4 SAS exome

AF:

0.0403

Gnomad4 FIN exome

AF:

0.0648

Gnomad4 NFE exome

AF:

0.0533

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0507

AC:

7713

AN:

152220

Hom.:

213

Cov.:

AF XY:

0.0499

AC XY:

3715

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0546

Gnomad4 AMR

AF:

0.0302

Gnomad4 ASJ

AF:

0.0822

Gnomad4 EAS

AF:

0.0332

Gnomad4 SAS

AF:

0.0429

Gnomad4 FIN

AF:

0.0637

Gnomad4 NFE

AF:

0.0513

Gnomad4 OTH

AF:

0.0455

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

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 26, 2017	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. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.90

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over