dbSNP rs138296448: MYF6:p.Ala90Asp (chr12-80707988-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 1P and 13B. PP3BP4BP6_Very_StrongBS2

The NM_002469.3(MYF6):c.269C>A(p.Ala90Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 1,614,102 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 3 hom. )

Consequence

MYF6
NM_002469.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.54

Publications

10 publications found

Variant links:

Genes affected

MYF6 (HGNC:7566): (myogenic factor 6) The protein encoded by this gene is a probable basic helix-loop-helix (bHLH) DNA binding protein involved in muscle differentiation. The encoded protein likely acts as a heterodimer with another bHLH protein. Defects in this gene are a cause of autosomal dominant centronuclear myopathy (ADCNM). [provided by RefSeq, May 2010]

MYF6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: AlphaMissense, BayesDel_noAF, Cadd, Eigen, phyloP100way_vertebrate, PrimateAI, REVEL, REVEL [when BayesDel_addAF, max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.36336333).

BP6

Variant 12-80707988-C-A is Benign according to our data. Variant chr12-80707988-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 472752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 130 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002469.3. 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
	MYF6	NM_002469.3	MANE Select	c.269C>A	p.Ala90Asp	missense	Exon 1 of 3	NP_002460.1	P23409

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYF6	ENST00000228641.4	TSL:1 MANE Select	c.269C>A	p.Ala90Asp	missense	Exon 1 of 3	ENSP00000228641.3	P23409
	MYF6	ENST00000957792.1		c.269C>A	p.Ala90Asp	missense	Exon 1 of 3	ENSP00000627851.1

Frequencies

GnomAD3 genomes

AF:

0.000854

AC:

130

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00146

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.000870

AC:

218

AN:

250682

AF XY:

0.000869

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000740

Gnomad NFE exome

AF:

0.00138

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00146

AC:

2137

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1012

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.000149

AC:

AN:

33480

American (AMR)

AF:

0.000894

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000612

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000487

AC:

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00177

AC:

1963

AN:

1112008

Other (OTH)

AF:

0.00144

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

222

296

370

<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:

0.000854

AC:

130

AN:

152264

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41542

American (AMR)

AF:

0.000784

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00146

AC:

AN:

68030

Other (OTH)

AF:

0.000947

AC:

AN:

2112

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:

0.000909

Hom.:

Bravo

AF:

0.000914

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.000758

AC:

EpiCase

AF:

0.00202

EpiControl

AF:

0.00107

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal dominant centronuclear myopathy (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Benign

0.0068

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.85

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.36

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.3

PhyloP100

7.5

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.5

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.032

Polyphen

1.0

Vest4

0.76

MVP

0.99

MPC

1.4

ClinPred

0.070

GERP RS

5.6

PromoterAI

-0.014

Neutral

(source)

Varity_R

0.87

gMVP

0.69

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over