NM_001042517.2:c.*147T>A

Variant names:

• chr13-59666437-A-T
• rs3803205
• NM_001042517.2:c.*147T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.
• 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 rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.*147T>A		3_prime_UTR_variant	Exon 28 of 28	ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.*147T>A		3_prime_UTR_variant	Exon 28 of 28	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.*147T>A		downstream_gene_variant		1		ENSP00000383173.1

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

African (AFR) AF: 0.600 AC: 10865 AN: 18122

American (AMR) AF: 0.654 AC: 12065 AN: 18452

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 11740 AN: 16378

East Asian (EAS) AF: 0.738 AC: 23519 AN: 31886

South Asian (SAS) AF: 0.644 AC: 29789 AN: 46256

European-Finnish (FIN) AF: 0.782 AC: 26483 AN: 33850

Middle Eastern (MID) AF: 0.651 AC: 1689 AN: 2596

European-Non Finnish (NFE) AF: 0.684 AC: 390543 AN: 571136

Other (OTH) AF: 0.676 AC: 24643 AN: 36468

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

African (AFR) AF: 0.603 AC: 24784 AN: 41080

American (AMR) AF: 0.653 AC: 9895 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2501 AN: 3468

East Asian (EAS) AF: 0.737 AC: 3782 AN: 5130

South Asian (SAS) AF: 0.638 AC: 3055 AN: 4788

European-Finnish (FIN) AF: 0.794 AC: 8019 AN: 10104

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.686 AC: 46561 AN: 67850

Other (OTH) AF: 0.649 AC: 1365 AN: 2104

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 31, 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
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.0
DANN	Benign	0.64
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3803205; hg19: chr13-60240571;