rs747131589

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_000260.4(MYO7A):c.6220C>T(p.Pro2074Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000758 in 1,582,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P2074H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000063 ( 0 hom. )

Consequence

MYO7A
NM_000260.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.51

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

nonsyndromic genetic hearing loss
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
autosomal recessive nonsyndromic hearing loss 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
Usher syndrome type 1
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, PanelApp Australia
Usher syndrome type 1B
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal dominant nonsyndromic hearing loss 11
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

MYO7A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3775288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO7A	NM_000260.4 link	c.6220C>T	p.Pro2074Ser	missense_variant	Exon 45 of 49	ENST00000409709.9	NP_000251.3	Q13402-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYO7A	ENST00000409709.9 link	c.6220C>T	p.Pro2074Ser	missense_variant	Exon 45 of 49	1	NM_000260.4	ENSP00000386331.3	Q13402-1
MYO7A	ENST00000458637.6 link	c.6106C>T	p.Pro2036Ser	missense_variant	Exon 45 of 49	1		ENSP00000392185.2	Q13402-2
MYO7A	ENST00000409619.6 link	c.6073C>T	p.Pro2025Ser	missense_variant	Exon 46 of 50	1		ENSP00000386635.2	Q13402-8
MYO7A	ENST00000458169.2 link	c.3646C>T	p.Pro1216Ser	missense_variant	Exon 25 of 29	1		ENSP00000417017.2	H7C4D8
MYO7A	ENST00000670577.1 link	n.*792C>T		non_coding_transcript_exon_variant	Exon 28 of 32			ENSP00000499323.1	A0A590UJ94
MYO7A	ENST00000670577.1 link	n.*792C>T		3_prime_UTR_variant	Exon 28 of 32			ENSP00000499323.1	A0A590UJ94

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000253

AC:

AN:

197744

AF XY:

0.0000188

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000629

AC:

AN:

1430316

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

708342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32832

American (AMR)

AF:

0.0000750

AC:

AN:

40000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25536

East Asian (EAS)

AF:

0.00

AC:

AN:

37902

South Asian (SAS)

AF:

0.0000246

AC:

AN:

81374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50952

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000365

AC:

AN:

1096692

Other (OTH)

AF:

0.00

AC:

AN:

59298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41442

American (AMR)

AF:

0.000131

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000167

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2

Uncertain:1

Jun 09, 2017

Counsyl

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

(source)

DANN

Benign

0.87

DEOGEN2

Uncertain

0.68

D;.;.;T

Eigen

Benign

-0.064

Eigen_PC

Benign

0.072

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Uncertain

0.092

MetaRNN

Benign

0.38

T;T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

2.0

M;.;.;.

PhyloP100

7.5

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-4.1

D;D;D;D

REVEL

Uncertain

0.45

Sift

Benign

0.46

T;T;T;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.099

B;.;.;.

Vest4

0.72

MutPred

0.35

Gain of MoRF binding (P = 0.0597);.;.;.;

MVP

0.85

MPC

0.44

ClinPred

0.62

GERP RS

5.2

Varity_R

0.61

gMVP

0.57

Mutation Taster

=25/75

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over