Genetic Variant NM_002469.3:c.*19C>A (chr12-80708979-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002469.3(MYF6):c.*19C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,562,002 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 38 hom., cov: 32)

Exomes 𝑓: 0.026 ( 596 hom. )

Consequence

MYF6
NM_002469.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.560

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 12-80708979-C-A is Benign according to our data. Variant chr12-80708979-C-A is described in ClinVar as Benign. ClinVar VariationId is 258665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0177 (2700/152336) while in subpopulation NFE AF = 0.0287 (1951/68028). AF 95% confidence interval is 0.0276. There are 38 homozygotes in GnomAd4. There are 1220 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2700 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.*19C>A		3_prime_UTR	Exon 3 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.*19C>A		3_prime_UTR	Exon 3 of 3	ENSP00000228641.3	P23409
	MYF6	ENST00000957792.1		c.*19C>A		3_prime_UTR	Exon 3 of 3	ENSP00000627851.1

Frequencies

GnomAD3 genomes

AF:

0.0177

AC:

2701

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00564

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0115

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0132

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.0198

AC:

4960

AN:

251062

AF XY:

0.0201

show subpopulations

Gnomad AFR exome

AF:

0.00604

Gnomad AMR exome

AF:

0.0116

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0152

Gnomad NFE exome

AF:

0.0296

Gnomad OTH exome

AF:

0.0233

GnomAD4 exome

AF:

0.0263

AC:

37041

AN:

1409666

Hom.:

596

Cov.:

AF XY:

0.0258

AC XY:

18194

AN XY:

704594

show subpopulations

African (AFR)

AF:

0.00439

AC:

142

AN:

32320

American (AMR)

AF:

0.0114

AC:

510

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00705

AC:

182

AN:

25808

East Asian (EAS)

AF:

0.00

AC:

AN:

39474

South Asian (SAS)

AF:

0.0178

AC:

1520

AN:

85176

European-Finnish (FIN)

AF:

0.0172

AC:

919

AN:

53374

Middle Eastern (MID)

AF:

0.00838

AC:

AN:

5610

European-Non Finnish (NFE)

AF:

0.0306

AC:

32533

AN:

1064600

Other (OTH)

AF:

0.0202

AC:

1188

AN:

58682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1790

3580

5371

7161

8951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1200

2400

3600

4800

6000

<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:

0.0177

AC:

2700

AN:

152336

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

1220

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00563

AC:

234

AN:

41586

American (AMR)

AF:

0.0114

AC:

175

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.0143

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0132

AC:

140

AN:

10626

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0287

AC:

1951

AN:

68028

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

133

266

400

533

666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0179

Hom.:

Bravo

AF:

0.0170

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

3.9

(source)

DANN

Benign

0.76

PhyloP100

-0.56

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over