Genetic Variant MYO7A:c.3924+31_3924+46dupAAGCACCTCCTCCCGG (chr11-77190879-G-GCCCGGAAGCACCTCCT) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP6_Very_Strong

The NM_000260.4(MYO7A):c.3924+31_3924+46dupAAGCACCTCCTCCCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000394 in 1,548,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

MYO7A
NM_000260.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0760

Variant links:

Genes affected

MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MYO7A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 11-77190879-G-GCCCGGAAGCACCTCCT is Benign according to our data. Variant chr11-77190879-G-GCCCGGAAGCACCTCCT is described in ClinVar as [Likely_benign]. Clinvar id is 227684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.3924+31_3924+46dupAAGCACCTCCTCCCGG		intron_variant	Intron 30 of 48	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.3924+31_3924+46dupAAGCACCTCCTCCCGG	intron_variant	Intron 30 of 48	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.3924+31_3924+46dupAAGCACCTCCTCCCGG	intron_variant	Intron 30 of 48	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.3891+31_3891+46dupAAGCACCTCCTCCCGG	intron_variant	Intron 31 of 49	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.1467+31_1467+46dupAAGCACCTCCTCCCGG	intron_variant	Intron 10 of 28	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.1764+31_1764+46dupAAGCACCTCCTCCCGG	intron_variant	Intron 13 of 31			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000176

AC:

AN:

170654

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91402

show subpopulations

Gnomad AFR exome

AF:

0.000103

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000278

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000358

AC:

AN:

1395858

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

686206

show subpopulations

Gnomad4 AFR exome

AF:

0.000189

Gnomad4 AMR exome

AF:

0.0000274

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000382

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Nov 09, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.3924+31_3924+46dup in intron 30 of MYO7A: This variant is not expected to have clinical significance because it is not located within the splice consensus seq uence and splice prediction tools do not suggest an impact to the canonical spli ce site. It has been identified in 5/19858 European chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org), though the ability of these studies to accurately detect indels may be limited. -

not provided

Benign:1

Feb 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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.

11-77190879-GCCCGGAAGCACCTCCT-GCCCGGAAGCACCTCCTCCCGGAAGCACCTCCT

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