rs73214504

Variant names:

• chr13-60016443-A-C
• rs73214504
• NM_001042517.2:c.627-298T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-60016443-A-C
• chr13-60016443-A-G
• chr13-60016443-A-T

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.627-298T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 152,174 control chromosomes in the GnomAD database, including 409 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.070 (409 hom., cov: 32)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.346
• Publications: 0 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 13-60016443-A-C is Benign according to our data. Variant chr13-60016443-A-C is described in ClinVar as Benign. ClinVar VariationId is 1282353.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 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.627-298T>G		intron	N/A	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.594-298T>G		intron	N/A	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.489-298T>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.627-298T>G		intron	N/A	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000377908.6	TSL:1	c.594-298T>G		intron	N/A	ENSP00000367141.2	Q9NSV4-4
	DIAPH3	ENST00000400320.5	TSL:1	c.489-298T>G		intron	N/A	ENSP00000383174.1	Q9NSV4-5

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10618 AN: 152056 Hom.: 405 Cov.: 32

Gnomad AFR AF: 0.0946

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.0549

Gnomad FIN AF: 0.0657

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0573

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

GnomAD4 genome AF: 0.0698 AC: 10625 AN: 152174 Hom.: 409 Cov.: 32 AF XY: 0.0705 AC XY: 5245 AN XY: 74406

African (AFR) AF: 0.0944 AC: 3919 AN: 41508

American (AMR) AF: 0.107 AC: 1628 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3472

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5176

South Asian (SAS) AF: 0.0543 AC: 262 AN: 4822

European-Finnish (FIN) AF: 0.0657 AC: 697 AN: 10604

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0535 AC: 3636 AN: 67998

Other (OTH) AF: 0.0562 AC: 119 AN: 2116

Alfa AF: 0.0360 Hom.: 35

Bravo AF: 0.0736

Asia WGS AF: 0.0510 AC: 176 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	2.6
DANN	Benign	0.60
PhyloP100		0.35
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: rs73214504; hg19: chr13-60590577;