13-60042494-C-CCTGAGCAATGTACCA

Position:

• chr13-60042494-C-CCTGAGCAATGTACCA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001042517.2(DIAPH3):​c.626+181_626+195dupTGGTACATTGCTCAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 152,060 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.010 (12 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0490

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-60042494-C-CCTGAGCAATGTACCA is Benign according to our data. Variant chr13-60042494-C-CCTGAGCAATGTACCA is described in ClinVar as [Likely_benign]. Clinvar id is 1195772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1592/152060) while in subpopulation NFE AF= 0.0181 (1230/67968). AF 95% confidence interval is 0.0173. There are 12 homozygotes in gnomad4. There are 703 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1592 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DIAPH3	NM_001042517.2	c.626+181_626+195dupTGGTACATTGCTCAG		intron_variant		ENST00000400324.9	NP_001035982.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DIAPH3	ENST00000400324.9	c.626+181_626+195dupTGGTACATTGCTCAG		intron_variant		1	NM_001042517.2	ENSP00000383178.3
DIAPH3	ENST00000400319.5	c.416+181_416+195dupTGGTACATTGCTCAG		intron_variant		1		ENSP00000383173.1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1592 AN: 151942 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00297

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.00715

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.00766

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

GnomAD4 genome AF: 0.0105 AC: 1592 AN: 152060 Hom.: 12 Cov.: 32 AF XY: 0.00946 AC XY: 703 AN XY: 74290

Gnomad4 AFR AF: 0.00296

Gnomad4 AMR AF: 0.00714

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.00360

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.0141 Hom.: 3

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs149246947; hg19: chr13-60616628;