13-60016165-C-T

Variant names:

• chr13-60016165-C-T
• rs2762134
• NM_001042517.2:c.627-20G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001042517.2(DIAPH3):​c.627-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 1,610,224 control chromosomes in the GnomAD database, including 444,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43395 hom., cov: 33)
  • Exomes 𝑓: 0.74 (401015 hom.)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.55
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 13-60016165-C-T is Benign according to our data. Variant chr13-60016165-C-T is described in ClinVar as Benign. ClinVar VariationId is 1255498.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 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.627-20G>A		intron	N/A	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.594-20G>A		intron	N/A	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.489-20G>A		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.627-20G>A		intron	N/A	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000377908.6	TSL:1	c.594-20G>A		intron	N/A	ENSP00000367141.2	Q9NSV4-4
	DIAPH3	ENST00000400320.5	TSL:1	c.489-20G>A		intron	N/A	ENSP00000383174.1	Q9NSV4-5

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114573 AN: 151898 Hom.: 43345 Cov.: 33

Gnomad AFR AF: 0.801

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.747

GnomAD2 exomes AF: 0.732 AC: 179396 AN: 245134 AF XY: 0.729

Gnomad AFR exome AF: 0.798

Gnomad AMR exome AF: 0.808

Gnomad ASJ exome AF: 0.739

Gnomad EAS exome AF: 0.627

Gnomad FIN exome AF: 0.666

Gnomad NFE exome AF: 0.732

Gnomad OTH exome AF: 0.719

GnomAD4 exome AF: 0.741 AC: 1080017 AN: 1458208 Hom.: 401015 Cov.: 35 AF XY: 0.739 AC XY: 536400 AN XY: 725420

African (AFR) AF: 0.796 AC: 26630 AN: 33434

American (AMR) AF: 0.808 AC: 36011 AN: 44576

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 19246 AN: 26036

East Asian (EAS) AF: 0.593 AC: 23476 AN: 39566

South Asian (SAS) AF: 0.722 AC: 62178 AN: 86062

European-Finnish (FIN) AF: 0.668 AC: 35562 AN: 53236

Middle Eastern (MID) AF: 0.689 AC: 3970 AN: 5764

European-Non Finnish (NFE) AF: 0.747 AC: 828234 AN: 1109306

Other (OTH) AF: 0.742 AC: 44710 AN: 60228

GnomAD4 genome AF: 0.754 AC: 114683 AN: 152016 Hom.: 43395 Cov.: 33 AF XY: 0.751 AC XY: 55784 AN XY: 74286

African (AFR) AF: 0.801 AC: 33226 AN: 41474

American (AMR) AF: 0.808 AC: 12342 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 2604 AN: 3470

East Asian (EAS) AF: 0.612 AC: 3161 AN: 5168

South Asian (SAS) AF: 0.729 AC: 3513 AN: 4816

European-Finnish (FIN) AF: 0.665 AC: 7000 AN: 10520

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.743 AC: 50482 AN: 67974

Other (OTH) AF: 0.745 AC: 1573 AN: 2112

Alfa AF: 0.752 Hom.: 15022

Bravo AF: 0.766

Asia WGS AF: 0.658 AC: 2293 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Autosomal dominant auditory neuropathy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.024
DANN	Benign	0.20
PhyloP100		-2.6
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: rs2762134; hg19: chr13-60590299; COSMIC: COSV57365133; COSMIC: COSV57365133;