NM_017433.5:c.409-16_409-15delAT

Variant names:

• chr10-25997137-TTA-T
• rs112520797
• NM_017433.5:c.409-16_409-15delAT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_017433.5(MYO3A):​c.409-16_409-15delAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,575,894 control chromosomes in the GnomAD database, including 1,752 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (174 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1578 hom.)
• Consequence: MYO3A NM_017433.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.06
• Publications: 1 publications found

Genes affected

MYO3A (HGNC:7601): (myosin IIIA) The protein encoded by this gene belongs to the myosin superfamily. Myosins are actin-dependent motor proteins and are categorized into conventional myosins (class II) and unconventional myosins (classes I and III through XV) based on their variable C-terminal cargo-binding domains. Class III myosins, such as this one, have a kinase domain N-terminal to the conserved N-terminal motor domains and are expressed in photoreceptors. The protein encoded by this gene plays an important role in hearing in humans. Three different recessive, loss of function mutations in the encoded protein have been shown to cause nonsyndromic progressive hearing loss. Expression of this gene is highly restricted, with the strongest expression in retina and cochlea. [provided by RefSeq, Jul 2008]

MYO3A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 30

  Inheritance: AR, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal dominant 90

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 10-25997137-TTA-T is Benign according to our data. Variant chr10-25997137-TTA-T is described in ClinVar as Benign. ClinVar VariationId is 164604.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017433.5. 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
	MYO3A	NM_017433.5	MANE Select	c.409-16_409-15delAT		intron	N/A	NP_059129.3
	MYO3A	NM_001368265.1		c.409-16_409-15delAT		intron	N/A	NP_001355194.1	Q8NEV4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	ENST00000642920.2	MANE Select	c.409-21_409-20delTA		intron	N/A	ENSP00000495965.1	Q8NEV4-1
	MYO3A	ENST00000543632.5	TSL:1	c.409-21_409-20delTA		intron	N/A	ENSP00000445909.1	F5H0U9
	MYO3A	ENST00000376302.5	TSL:1	c.409-21_409-20delTA		intron	N/A	ENSP00000365479.1	Q8NEV4-2

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 6517 AN: 152168 Hom.: 173 Cov.: 32

Gnomad AFR AF: 0.0398

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0277

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0405 AC: 10140 AN: 250424 AF XY: 0.0416

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.0255

Gnomad ASJ exome AF: 0.0570

Gnomad EAS exome AF: 0.00262

Gnomad FIN exome AF: 0.0365

Gnomad NFE exome AF: 0.0533

Gnomad OTH exome AF: 0.0413

GnomAD4 exome AF: 0.0437 AC: 62170 AN: 1423608 Hom.: 1578 AF XY: 0.0438 AC XY: 31123 AN XY: 710686

African (AFR) AF: 0.0389 AC: 1266 AN: 32504

American (AMR) AF: 0.0263 AC: 1176 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 1495 AN: 25908

East Asian (EAS) AF: 0.00135 AC: 53 AN: 39326

South Asian (SAS) AF: 0.0310 AC: 2643 AN: 85392

European-Finnish (FIN) AF: 0.0360 AC: 1919 AN: 53304

Middle Eastern (MID) AF: 0.0657 AC: 372 AN: 5664

European-Non Finnish (NFE) AF: 0.0471 AC: 50769 AN: 1077782

Other (OTH) AF: 0.0419 AC: 2477 AN: 59082

GnomAD4 genome AF: 0.0428 AC: 6512 AN: 152286 Hom.: 174 Cov.: 32 AF XY: 0.0412 AC XY: 3069 AN XY: 74472

African (AFR) AF: 0.0396 AC: 1647 AN: 41558

American (AMR) AF: 0.0368 AC: 562 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0576 AC: 200 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5188

South Asian (SAS) AF: 0.0277 AC: 134 AN: 4830

European-Finnish (FIN) AF: 0.0384 AC: 407 AN: 10612

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0500 AC: 3402 AN: 68020

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

Alfa AF: 0.0486 Hom.: 36

Bravo AF: 0.0428

Asia WGS AF: 0.0170 AC: 59 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.1
Mutation Taster		=99/1	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: rs112520797; hg19: chr10-26286066;