chr12-80708979-C-A

Variant names:

• chr12-80708979-C-A
• rs79738065
• NM_002469.3:c.*19C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.560
• Publications: 5 publications found

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

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYF6	NM_002469.3	c.*19C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000228641.4	NP_002460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYF6	ENST00000228641.4	c.*19C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_002469.3	ENSP00000228641.3

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2701 AN: 152218 Hom.: 38 Cov.: 32

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

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.: 26 AF XY: 0.0258 AC XY: 18194 AN XY: 704594

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: 0 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: 47 AN: 5610

European-Non Finnish (NFE) AF: 0.0306 AC: 32533 AN: 1064600

Other (OTH) AF: 0.0202 AC: 1188 AN: 58682

GnomAD4 genome AF: 0.0177 AC: 2700 AN: 152336 Hom.: 38 Cov.: 32 AF XY: 0.0164 AC XY: 1220 AN XY: 74494

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: 28 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4830

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1951 AN: 68028

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.0179 Hom.: 21

Bravo AF: 0.0170

Asia WGS AF: 0.00808 AC: 28 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.9
DANN	Benign	0.76
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs79738065; hg19: chr12-81102758;