Genetic Variant NM_002469.3:c.528T>C (chr12-80708532-T-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002469.3(MYF6):c.528T>C(p.Gly176Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000982 in 1,454,918 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 6 hom. )

Consequence

MYF6
NM_002469.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.840

Publications

1 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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 12-80708532-T-C is Benign according to our data. Variant chr12-80708532-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 435911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.84 with no splicing effect.

BS2

High AC in GnomAd4 at 96 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYF6	NM_002469.3	MANE Select	c.528T>C	p.Gly176Gly	synonymous	Exon 2 of 3	NP_002460.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYF6	ENST00000228641.4	TSL:1 MANE Select	c.528T>C	p.Gly176Gly	synonymous	Exon 2 of 3	ENSP00000228641.3

Frequencies

GnomAD3 genomes

AF:

0.000676

AC:

AN:

141964

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00267

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000255

Gnomad FIN

AF:

0.000110

Gnomad MID

AF:

0.00974

Gnomad NFE

AF:

0.000887

Gnomad OTH

AF:

0.00101

GnomAD2 exomes

AF:

0.000966

AC:

243

AN:

251446

AF XY:

0.000993

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000838

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.00102

AC:

1333

AN:

1312850

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

684

AN XY:

652286

show subpopulations

African (AFR)

AF:

0.000483

AC:

AN:

28976

American (AMR)

AF:

0.000970

AC:

AN:

40202

Ashkenazi Jewish (ASJ)

AF:

0.00453

AC:

AN:

20524

East Asian (EAS)

AF:

0.00

AC:

AN:

26114

South Asian (SAS)

AF:

0.000682

AC:

AN:

84988

European-Finnish (FIN)

AF:

0.000411

AC:

AN:

38914

Middle Eastern (MID)

AF:

0.0124

AC:

AN:

5008

European-Non Finnish (NFE)

AF:

0.000947

AC:

964

AN:

1017882

Other (OTH)

AF:

0.00173

AC:

AN:

50242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

140

211

281

351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.000676

AC:

AN:

142068

Hom.:

Cov.:

AF XY:

0.000536

AC XY:

AN XY:

69000

show subpopulations

African (AFR)

AF:

0.000181

AC:

AN:

38666

American (AMR)

AF:

0.00105

AC:

AN:

14268

Ashkenazi Jewish (ASJ)

AF:

0.00267

AC:

AN:

3372

East Asian (EAS)

AF:

0.00

AC:

AN:

4140

South Asian (SAS)

AF:

0.000254

AC:

AN:

3934

European-Finnish (FIN)

AF:

0.000110

AC:

AN:

9102

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000887

AC:

AN:

65416

Other (OTH)

AF:

0.00100

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00122

Hom.:

Bravo

AF:

0.000945

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00190

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MYF6: BP4, BP7

not specified

Benign:1

Jul 21, 2016

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Autosomal dominant centronuclear myopathy

Benign:1

Dec 06, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

8.0

(source)

DANN

Benign

0.59

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism

(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

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over