13-59857910-A-C

Variant names:

• chr13-59857910-A-C
• rs10507641
• NM_001042517.2:c.2737+3497T>G

Variant summary

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

The NM_001042517.2(DIAPH3):​c.2737+3497T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 152,240 control chromosomes in the GnomAD database, including 307 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 0.058 (307 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.25
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042517.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	NM_001042517.2	MANE Select	c.2737+3497T>G		intron	N/A	NP_001035982.1
	DIAPH3	NM_001258366.2		c.2704+3497T>G		intron	N/A	NP_001245295.1
	DIAPH3	NM_001258367.2		c.2599+3497T>G		intron	N/A	NP_001245296.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	ENST00000400324.9	TSL:1 MANE Select	c.2737+3497T>G		intron	N/A	ENSP00000383178.3
	DIAPH3	ENST00000377908.6	TSL:1	c.2704+3497T>G		intron	N/A	ENSP00000367141.2
	DIAPH3	ENST00000400320.5	TSL:1	c.2599+3497T>G		intron	N/A	ENSP00000383174.1

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8814 AN: 152122 Hom.: 303 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0395

Gnomad SAS AF: 0.0543

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0492

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

GnomAD4 genome AF: 0.0579 AC: 8821 AN: 152240 Hom.: 307 Cov.: 32 AF XY: 0.0591 AC XY: 4397 AN XY: 74426

African (AFR) AF: 0.0533 AC: 2215 AN: 41564

American (AMR) AF: 0.100 AC: 1532 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3466

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5174

South Asian (SAS) AF: 0.0537 AC: 259 AN: 4822

European-Finnish (FIN) AF: 0.0660 AC: 700 AN: 10610

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.0537 AC: 3652 AN: 68020

Other (OTH) AF: 0.0482 AC: 102 AN: 2116

Alfa AF: 0.0531 Hom.: 254

Bravo AF: 0.0596

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		2.2
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: rs10507641; hg19: chr13-60432044;