rs145205388

Positions:

• chr12-80708532-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.840

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYF6	NM_002469.3	c.528T>C	p.Gly176Gly	synonymous_variant	2/3	ENST00000228641.4	NP_002460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYF6	ENST00000228641.4	c.528T>C	p.Gly176Gly	synonymous_variant	2/3	1	NM_002469.3	ENSP00000228641.3

Frequencies

GnomAD3 genomes AF: 0.000676 AC: 96 AN: 141964 Hom.: 0 Cov.: 32

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

GnomAD3 exomes AF: 0.000966 AC: 243 AN: 251446 Hom.: 2 AF XY: 0.000993 AC XY: 135 AN XY: 135910

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 SAS exome AF: 0.000490

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.: 6 Cov.: 33 AF XY: 0.00105 AC XY: 684 AN XY: 652286

Gnomad4 AFR exome AF: 0.000483

Gnomad4 AMR exome AF: 0.000970

Gnomad4 ASJ exome AF: 0.00453

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000682

Gnomad4 FIN exome AF: 0.000411

Gnomad4 NFE exome AF: 0.000947

Gnomad4 OTH exome AF: 0.00173

GnomAD4 genome AF: 0.000676 AC: 96 AN: 142068 Hom.: 0 Cov.: 32 AF XY: 0.000536 AC XY: 37 AN XY: 69000

Gnomad4 AFR AF: 0.000181

Gnomad4 AMR AF: 0.00105

Gnomad4 ASJ AF: 0.00267

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000254

Gnomad4 FIN AF: 0.000110

Gnomad4 NFE AF: 0.000887

Gnomad4 OTH AF: 0.00100

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.000945

Asia WGS AF: 0.000289 AC: 1 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

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	MYF6: BP4, BP7 -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 21, 2016

- -

Autosomal dominant centronuclear myopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 06, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.0
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs145205388; hg19: chr12-81102311;