rs56210104

Variant names:

• chr10-26021668-G-A
• rs56210104
• ENST00000376302.5:c.*7G>A

Variant summary

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

The ENST00000376302.5(MYO3A):​c.*7G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,613,526 control chromosomes in the GnomAD database, including 6,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.066 (417 hom., cov: 32)
  • Exomes 𝑓: 0.084 (5769 hom.)
• Consequence: MYO3A ENST00000376302.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.336
• Publications: 2 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), PanelApp Australia, 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 10-26021668-G-A is Benign according to our data. Variant chr10-26021668-G-A is described in ClinVar as Benign. ClinVar VariationId is 260812.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000376302.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	NM_017433.5	MANE Select	c.731+20G>A		intron	N/A	NP_059129.3
	MYO3A	NM_001368265.1		c.*7G>A		3_prime_UTR	Exon 8 of 8	NP_001355194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO3A	ENST00000376302.5	TSL:1	c.*7G>A		3_prime_UTR	Exon 8 of 8	ENSP00000365479.1
	MYO3A	ENST00000642920.2	MANE Select	c.731+20G>A		intron	N/A	ENSP00000495965.1
	MYO3A	ENST00000543632.5	TSL:1	c.731+20G>A		intron	N/A	ENSP00000445909.1

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10094 AN: 152102 Hom.: 416 Cov.: 32

Gnomad AFR AF: 0.0277

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0940

Gnomad OTH AF: 0.0738

GnomAD2 exomes AF: 0.0674 AC: 16943 AN: 251272 AF XY: 0.0683

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.0520

Gnomad ASJ exome AF: 0.0926

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.0699

Gnomad NFE exome AF: 0.0949

Gnomad OTH exome AF: 0.0797

GnomAD4 exome AF: 0.0844 AC: 123400 AN: 1461306 Hom.: 5769 Cov.: 34 AF XY: 0.0832 AC XY: 60508 AN XY: 726992

African (AFR) AF: 0.0257 AC: 860 AN: 33472

American (AMR) AF: 0.0547 AC: 2445 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0918 AC: 2397 AN: 26124

East Asian (EAS) AF: 0.000277 AC: 11 AN: 39692

South Asian (SAS) AF: 0.0330 AC: 2850 AN: 86252

European-Finnish (FIN) AF: 0.0734 AC: 3916 AN: 53380

Middle Eastern (MID) AF: 0.0489 AC: 282 AN: 5766

European-Non Finnish (NFE) AF: 0.0953 AC: 105894 AN: 1111520

Other (OTH) AF: 0.0786 AC: 4745 AN: 60378

GnomAD4 genome AF: 0.0663 AC: 10095 AN: 152220 Hom.: 417 Cov.: 32 AF XY: 0.0645 AC XY: 4802 AN XY: 74412

African (AFR) AF: 0.0276 AC: 1147 AN: 41544

American (AMR) AF: 0.0755 AC: 1154 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 339 AN: 3470

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

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4828

European-Finnish (FIN) AF: 0.0691 AC: 732 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6389 AN: 68006

Other (OTH) AF: 0.0739 AC: 156 AN: 2110

Alfa AF: 0.0810 Hom.: 253

Bravo AF: 0.0665

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Autosomal recessive nonsyndromic hearing loss 30 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: -20

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56210104; hg19: chr10-26310597;