rs35010955

Variant names:

• chr10-26021541-C-T
• rs35010955
• NM_017433.5:c.624C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-26021541-C-T
• chr10-26021541-C-A
• chr10-26021541-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_017433.5(MYO3A):​c.624C>T​(p.Asp208Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 1,613,856 control chromosomes in the GnomAD database, including 6,413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (514 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5899 hom.)
• Consequence: MYO3A NM_017433.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 2.73
• Publications: 10 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 10-26021541-C-T is Benign according to our data. Variant chr10-26021541-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.73 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0925 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.624C>T	p.Asp208Asp	synonymous	Exon 8 of 35	NP_059129.3
	MYO3A	NM_001368265.1		c.624C>T	p.Asp208Asp	synonymous	Exon 8 of 8	NP_001355194.1	Q8NEV4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	ENST00000642920.2	MANE Select	c.624C>T	p.Asp208Asp	synonymous	Exon 8 of 35	ENSP00000495965.1	Q8NEV4-1
	MYO3A	ENST00000543632.5	TSL:1	c.624C>T	p.Asp208Asp	synonymous	Exon 7 of 17	ENSP00000445909.1	F5H0U9
	MYO3A	ENST00000376302.5	TSL:1	c.624C>T	p.Asp208Asp	synonymous	Exon 8 of 8	ENSP00000365479.1	Q8NEV4-2

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11837 AN: 152076 Hom.: 511 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.0978

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0692

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.0794

GnomAD2 exomes AF: 0.0707 AC: 17779 AN: 251384 AF XY: 0.0709

Gnomad AFR exome AF: 0.0671

Gnomad AMR exome AF: 0.0557

Gnomad ASJ exome AF: 0.0928

Gnomad EAS exome AF: 0.000598

Gnomad FIN exome AF: 0.0701

Gnomad NFE exome AF: 0.0952

Gnomad OTH exome AF: 0.0808

GnomAD4 exome AF: 0.0859 AC: 125527 AN: 1461662 Hom.: 5899 Cov.: 35 AF XY: 0.0845 AC XY: 61451 AN XY: 727144

African (AFR) AF: 0.0664 AC: 2224 AN: 33480

American (AMR) AF: 0.0588 AC: 2628 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0918 AC: 2400 AN: 26134

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39698

South Asian (SAS) AF: 0.0332 AC: 2865 AN: 86256

European-Finnish (FIN) AF: 0.0736 AC: 3929 AN: 53416

Middle Eastern (MID) AF: 0.0505 AC: 291 AN: 5768

European-Non Finnish (NFE) AF: 0.0956 AC: 106252 AN: 1111794

Other (OTH) AF: 0.0815 AC: 4922 AN: 60392

GnomAD4 genome AF: 0.0778 AC: 11845 AN: 152194 Hom.: 514 Cov.: 32 AF XY: 0.0762 AC XY: 5668 AN XY: 74398

African (AFR) AF: 0.0647 AC: 2688 AN: 41520

American (AMR) AF: 0.0861 AC: 1316 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0978 AC: 339 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0288 AC: 139 AN: 4820

European-Finnish (FIN) AF: 0.0692 AC: 733 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0944 AC: 6420 AN: 68004

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.0868 Hom.: 395

Bravo AF: 0.0793

Asia WGS AF: 0.0340 AC: 120 AN: 3478

EpiCase AF: 0.0930

EpiControl AF: 0.103

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Autosomal recessive nonsyndromic hearing loss 30 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	13
DANN	Benign	0.56
PhyloP100		2.7
Mutation Taster		=91/9	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs35010955; hg19: chr10-26310470;