13-60016416-G-C

Variant names:

• chr13-60016416-G-C
• rs386809
• NM_001042517.2:c.627-271C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001042517.2(DIAPH3):​c.627-271C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,986 control chromosomes in the GnomAD database, including 4,075 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4075 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.407
• Publications: 4 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-AS1 (HGNC:39915): (DIAPH3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-60016416-G-C is Benign according to our data. Variant chr13-60016416-G-C is described in ClinVar as Benign. ClinVar VariationId is 1181901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.262 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	NM_001042517.2	MANE Select	c.627-271C>G		intron	N/A	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.594-271C>G		intron	N/A	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.489-271C>G		intron	N/A	NP_001245296.1	Q9NSV4-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DIAPH3	ENST00000400324.9	TSL:1 MANE Select	c.627-271C>G		intron	N/A	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000377908.6	TSL:1	c.594-271C>G		intron	N/A	ENSP00000367141.2	Q9NSV4-4
	DIAPH3	ENST00000400320.5	TSL:1	c.489-271C>G		intron	N/A	ENSP00000383174.1	Q9NSV4-5

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34402 AN: 151868 Hom.: 4076 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.226 AC: 34423 AN: 151986 Hom.: 4075 Cov.: 32 AF XY: 0.223 AC XY: 16531 AN XY: 74280

African (AFR) AF: 0.211 AC: 8751 AN: 41442

American (AMR) AF: 0.194 AC: 2967 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.107 AC: 553 AN: 5170

South Asian (SAS) AF: 0.275 AC: 1322 AN: 4814

European-Finnish (FIN) AF: 0.187 AC: 1970 AN: 10562

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.254 AC: 17258 AN: 67954

Other (OTH) AF: 0.239 AC: 502 AN: 2104

Alfa AF: 0.121 Hom.: 218

Bravo AF: 0.225

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.52
DANN	Benign	0.43
PhyloP100		-0.41
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: rs386809; hg19: chr13-60590550;