13-60015851-C-T

Variant names:

• chr13-60015851-C-T
• rs41293426
• NM_001042517.2:c.771+62G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001042517.2(DIAPH3):​c.771+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 1,399,480 control chromosomes in the GnomAD database, including 582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (49 hom., cov: 32)
  • Exomes 𝑓: 0.027 (533 hom.)
• Consequence: DIAPH3 NM_001042517.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.170
• Publications: 2 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=-0.81).
• BP6: Variant 13-60015851-C-T is Benign according to our data. Variant chr13-60015851-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1198319.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0203 (3087/152246) while in subpopulation NFE AF = 0.0318 (2162/68014). AF 95% confidence interval is 0.0307. There are 49 homozygotes in GnomAd4. There are 1426 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 3087 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+62G>A		intron	N/A	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.738+62G>A		intron	N/A	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.633+62G>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.771+62G>A		intron	N/A	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000377908.6	TSL:1	c.738+62G>A		intron	N/A	ENSP00000367141.2	Q9NSV4-4
	DIAPH3	ENST00000400320.5	TSL:1	c.633+62G>A		intron	N/A	ENSP00000383174.1	Q9NSV4-5

Frequencies

GnomAD3 genomes AF: 0.0203 AC: 3086 AN: 152128 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00567

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0261

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00684

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0318

Gnomad OTH AF: 0.0201

GnomAD4 exome AF: 0.0273 AC: 34039 AN: 1247234 Hom.: 533 AF XY: 0.0272 AC XY: 17103 AN XY: 629514

African (AFR) AF: 0.00458 AC: 133 AN: 29016

American (AMR) AF: 0.0199 AC: 841 AN: 42316

Ashkenazi Jewish (ASJ) AF: 0.0383 AC: 942 AN: 24586

East Asian (EAS) AF: 0.0000523 AC: 2 AN: 38268

South Asian (SAS) AF: 0.00841 AC: 674 AN: 80136

European-Finnish (FIN) AF: 0.00684 AC: 354 AN: 51752

Middle Eastern (MID) AF: 0.0291 AC: 110 AN: 3784

European-Non Finnish (NFE) AF: 0.0319 AC: 29522 AN: 924448

Other (OTH) AF: 0.0276 AC: 1461 AN: 52928

GnomAD4 genome AF: 0.0203 AC: 3087 AN: 152246 Hom.: 49 Cov.: 32 AF XY: 0.0192 AC XY: 1426 AN XY: 74440

African (AFR) AF: 0.00566 AC: 235 AN: 41534

American (AMR) AF: 0.0260 AC: 398 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00684 AC: 33 AN: 4824

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10608

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0318 AC: 2162 AN: 68014

Other (OTH) AF: 0.0199 AC: 42 AN: 2114

Alfa AF: 0.0290 Hom.: 92

Bravo AF: 0.0223

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.5
DANN	Benign	0.72
PhyloP100		0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs41293426; hg19: chr13-60589985;