chr13-59857910-A-C

Position:

• chr13-59857910-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DIAPH3	NM_001042517.2	c.2737+3497T>G		intron_variant		ENST00000400324.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DIAPH3	ENST00000400324.9	c.2737+3497T>G		intron_variant		1	NM_001042517.2	P2

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

Gnomad4 AFR AF: 0.0533

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.0394

Gnomad4 SAS AF: 0.0537

Gnomad4 FIN AF: 0.0660

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0482

Alfa AF: 0.0515 Hom.: 185

Bravo AF: 0.0596

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs10507641; hg19: chr13-60432044;