13-60015625-A-G

Variant names:

• chr13-60015625-A-G
• rs147157689
• NM_001042517.2:c.771+288T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001042517.2(DIAPH3):​c.771+288T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 149,118 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0038 (4 hom., cov: 31)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-60015625-A-G is Benign according to our data. Variant chr13-60015625-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1203527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 570 AD,Unknown gene.

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.771+288T>C		intron	N/A	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.738+288T>C		intron	N/A	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.633+288T>C		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.771+288T>C		intron	N/A	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000377908.6	TSL:1	c.738+288T>C		intron	N/A	ENSP00000367141.2	Q9NSV4-4
	DIAPH3	ENST00000400320.5	TSL:1	c.633+288T>C		intron	N/A	ENSP00000383174.1	Q9NSV4-5

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 570 AN: 149000 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000934

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000446

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00382 AC: 570 AN: 149118 Hom.: 4 Cov.: 31 AF XY: 0.00393 AC XY: 286 AN XY: 72798

African (AFR) AF: 0.0135 AC: 553 AN: 40820

American (AMR) AF: 0.000932 AC: 14 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3430

East Asian (EAS) AF: 0.00 AC: 0 AN: 4890

South Asian (SAS) AF: 0.00 AC: 0 AN: 4570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9868

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000446 AC: 3 AN: 67254

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00580 Hom.: 2

ClinVar

ClinVar submissions

Significance: Likely 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	-0.84
CADD	Benign	0.43
DANN	Benign	0.55
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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: rs147157689; hg19: chr13-60589759;