chr13-59854867-T-C

Variant names:

• chr13-59854867-T-C
• rs341497
• NM_001042517.2:c.2737+6540A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001042517.2(DIAPH3):​c.2737+6540A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,216 control chromosomes in the GnomAD database, including 956 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 0.091 (956 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.2737+6540A>G		intron_variant	Intron 22 of 27	ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.2737+6540A>G		intron_variant	Intron 22 of 27	1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.2527+6540A>G		intron_variant	Intron 20 of 25	1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13838 AN: 152098 Hom.: 960 Cov.: 32

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0784

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0664

Gnomad OTH AF: 0.0863

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

GnomAD4 genome AF: 0.0909 AC: 13829 AN: 152216 Hom.: 956 Cov.: 32 AF XY: 0.0972 AC XY: 7231 AN XY: 74426

African (AFR) AF: 0.0828 AC: 3437 AN: 41532

American (AMR) AF: 0.0736 AC: 1125 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0784 AC: 272 AN: 3470

East Asian (EAS) AF: 0.402 AC: 2078 AN: 5170

South Asian (SAS) AF: 0.144 AC: 693 AN: 4824

European-Finnish (FIN) AF: 0.136 AC: 1447 AN: 10602

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0664 AC: 4519 AN: 68016

Other (OTH) AF: 0.0868 AC: 183 AN: 2108

Alfa AF: 0.0757 Hom.: 1800

Bravo AF: 0.0877

Asia WGS AF: 0.264 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	20
DANN	Benign	0.73
PhyloP100		1.7
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: rs341497; hg19: chr13-60429001;