Variant 10-25934244-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_017433.5(MYO3A):c.-189C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 152,332 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 58 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYO3A
NM_017433.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.09

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-25934244-C-G is Benign according to our data. Variant chr10-25934244-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 299638.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1964/152332) while in subpopulation AFR AF= 0.0447 (1859/41588). AF 95% confidence interval is 0.043. There are 58 homozygotes in gnomad4. There are 919 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO3A	NM_017433.5 linkuse as main transcript	c.-189C>G		5_prime_UTR_variant	1/35	ENST00000642920.2	NP_059129.3

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO3A	ENST00000642920.2 linkuse as main transcript	c.-189C>G	5_prime_UTR_variant	1/35		NM_017433.5	ENSP00000495965	P1	Q8NEV4-1
MYO3A	ENST00000642197.1 linkuse as main transcript	n.16C>G	non_coding_transcript_exon_variant	1/27
MYO3A	ENST00000376302.5 linkuse as main transcript		upstream_gene_variant		1		ENSP00000365479		Q8NEV4-2

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1962

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0448

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00405

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0115

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

252

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

202

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0129

AC:

1964

AN:

152332

Hom.:

Cov.:

AF XY:

0.0123

AC XY:

919

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0447

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.00231

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 30

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.1

DANN

Benign

0.50

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over