13-59666357-CAAAAAA-CAAAAAAA

Variant names:

• chr13-59666357-C-CA
• rs11421911
• NM_001042517.2:c.*226dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001042517.2(DIAPH3):​c.*226dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (17401 hom., cov: 0)
  • Exomes 𝑓: 0.24 (39 hom.)
• Consequence: DIAPH3 NM_001042517.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.612
• 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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• auditory neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• autosomal dominant auditory neuropathy 1

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-59666357-C-CA is Benign according to our data. Variant chr13-59666357-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1282927.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 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.*226dupT		3_prime_UTR	Exon 28 of 28	NP_001035982.1	Q9NSV4-3
	DIAPH3	NM_001258366.2		c.*226dupT		3_prime_UTR	Exon 27 of 27	NP_001245295.1	Q9NSV4-4
	DIAPH3	NM_001258367.2		c.*226dupT		3_prime_UTR	Exon 26 of 26	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.*226dupT		3_prime_UTR	Exon 28 of 28	ENSP00000383178.3	Q9NSV4-3
	DIAPH3	ENST00000649952.1		n.672dupT		non_coding_transcript_exon	Exon 2 of 2
	DIAPH3	ENST00000377908.6	TSL:1	c.*226dupT		downstream_gene	N/A	ENSP00000367141.2	Q9NSV4-4

Frequencies

GnomAD3 genomes AF: 0.593 AC: 66325 AN: 111846 Hom.: 17407 Cov.: 0

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.555

GnomAD4 exome AF: 0.241 AC: 45553 AN: 189138 Hom.: 39 Cov.: 0 AF XY: 0.239 AC XY: 23822 AN XY: 99600

African (AFR) AF: 0.206 AC: 949 AN: 4600

American (AMR) AF: 0.240 AC: 1580 AN: 6580

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 1432 AN: 5982

East Asian (EAS) AF: 0.203 AC: 2265 AN: 11142

South Asian (SAS) AF: 0.222 AC: 3897 AN: 17586

European-Finnish (FIN) AF: 0.271 AC: 2411 AN: 8910

Middle Eastern (MID) AF: 0.201 AC: 183 AN: 912

European-Non Finnish (NFE) AF: 0.247 AC: 30211 AN: 122202

Other (OTH) AF: 0.234 AC: 2625 AN: 11224

GnomAD4 genome AF: 0.593 AC: 66307 AN: 111830 Hom.: 17401 Cov.: 0 AF XY: 0.591 AC XY: 31124 AN XY: 52622

African (AFR) AF: 0.486 AC: 14108 AN: 29010

American (AMR) AF: 0.610 AC: 6575 AN: 10786

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 1728 AN: 2868

East Asian (EAS) AF: 0.542 AC: 1986 AN: 3664

South Asian (SAS) AF: 0.571 AC: 1897 AN: 3324

European-Finnish (FIN) AF: 0.671 AC: 3060 AN: 4560

Middle Eastern (MID) AF: 0.564 AC: 115 AN: 204

European-Non Finnish (NFE) AF: 0.642 AC: 35383 AN: 55084

Other (OTH) AF: 0.553 AC: 831 AN: 1504

Alfa AF: 0.00 Hom.: 0

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
PhyloP100		-0.61
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: rs11421911; hg19: chr13-60240491; COSMIC: COSV64958480; COSMIC: COSV64958480;