13-59977280-T-C

Position:

• chr13-59977280-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001042517.2(DIAPH3):​c.1546-2824A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,632 control chromosomes in the GnomAD database, including 43,201 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 0.75 (43201 hom., cov: 31)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.1546-2824A>G		intron_variant		ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.1546-2824A>G		intron_variant		1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.1336-2824A>G		intron_variant		1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114210 AN: 151514 Hom.: 43162 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.754 AC: 114310 AN: 151632 Hom.: 43201 Cov.: 31 AF XY: 0.750 AC XY: 55592 AN XY: 74080

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.747

Alfa AF: 0.746 Hom.: 19494

Bravo AF: 0.765

Asia WGS AF: 0.657 AC: 2289 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.69

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: rs339536; hg19: chr13-60551414;