rs141278987

Variant names:

• chr12-80708548-A-C
• rs141278987
• NM_002469.3:c.544A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-80708548-A-C
• chr12-80708548-A-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_002469.3(MYF6):​c.544A>C​(p.Thr182Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000484 in 1,576,370 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0027 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: MYF6 NM_002469.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 4.07
• Publications: 1 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012334496).
• BP6: Variant 12-80708548-A-C is Benign according to our data. Variant chr12-80708548-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 472757.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 394 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.544A>C	p.Thr182Pro	missense	Exon 2 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.544A>C	p.Thr182Pro	missense	Exon 2 of 3	ENSP00000228641.3	P23409
	MYF6	ENST00000957792.1		c.544A>C	p.Thr182Pro	missense	Exon 2 of 3	ENSP00000627851.1

Frequencies

GnomAD3 genomes AF: 0.00264 AC: 391 AN: 148190 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00918

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000970

GnomAD2 exomes AF: 0.000672 AC: 169 AN: 251476 AF XY: 0.000493

Gnomad AFR exome AF: 0.00911

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000258 AC: 369 AN: 1428048 Hom.: 2 Cov.: 33 AF XY: 0.000232 AC XY: 165 AN XY: 710530

African (AFR) AF: 0.00980 AC: 318 AN: 32434

American (AMR) AF: 0.000572 AC: 25 AN: 43672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24834

East Asian (EAS) AF: 0.00 AC: 0 AN: 36976

South Asian (SAS) AF: 0.0000233 AC: 2 AN: 85960

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1091084

Other (OTH) AF: 0.000361 AC: 21 AN: 58122

GnomAD4 genome AF: 0.00266 AC: 394 AN: 148322 Hom.: 2 Cov.: 32 AF XY: 0.00258 AC XY: 187 AN XY: 72442

African (AFR) AF: 0.00925 AC: 376 AN: 40638

American (AMR) AF: 0.00107 AC: 16 AN: 14938

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3444

East Asian (EAS) AF: 0.00 AC: 0 AN: 4670

South Asian (SAS) AF: 0.00 AC: 0 AN: 4380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9942

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67042

Other (OTH) AF: 0.000961 AC: 2 AN: 2082

Alfa AF: 0.00121 Hom.: 2

Bravo AF: 0.00301

ExAC AF: 0.000684 AC: 83

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant centronuclear myopathy (1)
-	-	1	MYF6-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T
Eigen	Benign	0.016
Eigen_PC	Benign	0.0019
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.50	T
MetaRNN	Benign	0.012	T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.23	N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.018	D
Sift4G	Benign	0.21	T
Polyphen		0.92	P
Vest4		0.59
MVP		0.99
MPC		0.95
ClinPred		0.029	T
GERP RS		4.2
Varity_R		0.21
gMVP		0.23
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141278987; hg19: chr12-81102327; COSMIC: COSV57352335;