12-80708071-C-A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_002469.3(MYF6):​c.352C>A​(p.Arg118Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,614,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

MYF6
NM_002469.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.29

Publications

2 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 12-80708071-C-A is Benign according to our data. Variant chr12-80708071-C-A is described in ClinVar as [Benign]. Clinvar id is 472755.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.29 with no splicing effect.
BS2
High AC in GnomAd4 at 317 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYF6NM_002469.3 linkc.352C>A p.Arg118Arg synonymous_variant Exon 1 of 3 ENST00000228641.4 NP_002460.1 P23409

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYF6ENST00000228641.4 linkc.352C>A p.Arg118Arg synonymous_variant Exon 1 of 3 1 NM_002469.3 ENSP00000228641.3 P23409

Frequencies

GnomAD3 genomes
AF:
0.00208
AC:
317
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00697
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000851
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.000955
GnomAD2 exomes
AF:
0.000526
AC:
132
AN:
251138
AF XY:
0.000368
show subpopulations
Gnomad AFR exome
AF:
0.00573
Gnomad AMR exome
AF:
0.000549
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000462
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.000489
GnomAD4 exome
AF:
0.000257
AC:
375
AN:
1461888
Hom.:
1
Cov.:
31
AF XY:
0.000249
AC XY:
181
AN XY:
727242
show subpopulations
African (AFR)
AF:
0.00517
AC:
173
AN:
33480
American (AMR)
AF:
0.000604
AC:
27
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.0000383
AC:
1
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.0000116
AC:
1
AN:
86258
European-Finnish (FIN)
AF:
0.000225
AC:
12
AN:
53414
Middle Eastern (MID)
AF:
0.00121
AC:
7
AN:
5768
European-Non Finnish (NFE)
AF:
0.000116
AC:
129
AN:
1112012
Other (OTH)
AF:
0.000414
AC:
25
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.473
Heterozygous variant carriers
0
29
57
86
114
143
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00208
AC:
317
AN:
152266
Hom.:
0
Cov.:
32
AF XY:
0.00202
AC XY:
150
AN XY:
74440
show subpopulations
African (AFR)
AF:
0.00695
AC:
289
AN:
41560
American (AMR)
AF:
0.000850
AC:
13
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5150
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.0000942
AC:
1
AN:
10614
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.000176
AC:
12
AN:
68028
Other (OTH)
AF:
0.000945
AC:
2
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
18
36
55
73
91
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
10
20
30
40
50
<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:
0.000605
Hom.:
0
Bravo
AF:
0.00218
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal dominant centronuclear myopathy Benign:1
Aug 30, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
9.4
DANN
Benign
0.93
PhyloP100
1.3
PromoterAI
0.015
Neutral

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

Other links and lift over

dbSNP: rs34563783; hg19: chr12-81101850; API