NM_001042517.2:c.391-2381G>A

Variant names:

• chr13-60096113-C-T
• rs10507647
• NM_001042517.2:c.391-2381G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042517.2(DIAPH3):​c.391-2381G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0634 in 152,056 control chromosomes in the GnomAD database, including 459 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.063 (459 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.391-2381G>A		intron_variant	Intron 3 of 27	ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.391-2381G>A		intron_variant	Intron 3 of 27	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.181-2381G>A		intron_variant	Intron 1 of 25	1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.0634 AC: 9632 AN: 151940 Hom.: 458 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0710

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0657

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0634 AC: 9636 AN: 152056 Hom.: 459 Cov.: 32 AF XY: 0.0633 AC XY: 4702 AN XY: 74320

African (AFR) AF: 0.0473 AC: 1962 AN: 41484

American (AMR) AF: 0.0465 AC: 711 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0671 AC: 233 AN: 3470

East Asian (EAS) AF: 0.287 AC: 1482 AN: 5162

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4822

European-Finnish (FIN) AF: 0.0710 AC: 750 AN: 10560

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0602 AC: 4091 AN: 67966

Other (OTH) AF: 0.0655 AC: 138 AN: 2108

Alfa AF: 0.0661 Hom.: 220

Bravo AF: 0.0613

Asia WGS AF: 0.143 AC: 496 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.42
PhyloP100		-0.031
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: rs10507647; hg19: chr13-60670247;