rs34563783

Variant names:

• chr12-80708071-C-A
• rs34563783
• NM_002469.3:c.352C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-80708071-C-A
• chr12-80708071-C-G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29
• Publications: 2 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 -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 VariationId 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.

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.352C>A	p.Arg118Arg	synonymous	Exon 1 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.352C>A	p.Arg118Arg	synonymous	Exon 1 of 3	ENSP00000228641.3	P23409
	MYF6	ENST00000957792.1		c.352C>A	p.Arg118Arg	synonymous	Exon 1 of 3	ENSP00000627851.1

Frequencies

GnomAD3 genomes AF: 0.00208 AC: 317 AN: 152148 Hom.: 0 Cov.: 32

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

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

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

GnomAD4 genome AF: 0.00208 AC: 317 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.00202 AC XY: 150 AN XY: 74440

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

Alfa AF: 0.000605 Hom.: 0

Bravo AF: 0.00218

EpiCase AF: 0.000218

EpiControl AF: 0.000178

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant centronuclear myopathy (1)

Computational scores

Source: dbNSFP v4.9

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

Other links and lift over

dbSNP: rs34563783; hg19: chr12-81101850;