Variant 12-80717524-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005593.3(MYF5):c.461C>G(p.Ser154Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

MYF5
NM_005593.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.53

Variant links:

Genes affected

MYF5 (HGNC:7565): (myogenic factor 5) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to contribute to E-box binding activity. Predicted to be involved in several processes, including muscle cell fate commitment; positive regulation of cell differentiation; and skeletal muscle cell differentiation. Predicted to act upstream of or within several processes, including animal organ development; regulation of cell-matrix adhesion; and somitogenesis. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MYF5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.852

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYF5	NM_005593.3 linkuse as main transcript	c.461C>G	p.Ser154Trp	missense_variant	1/3	ENST00000228644.4	NP_005584.2	P13349

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYF5	ENST00000228644.4 linkuse as main transcript	c.461C>G	p.Ser154Trp	missense_variant	1/3	1	NM_005593.3	ENSP00000228644.3		P13349

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251234

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000659

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2023

The c.461C>G (p.S154W) alteration is located in exon 1 (coding exon 1) of the MYF5 gene. This alteration results from a C to G substitution at nucleotide position 461, causing the serine (S) at amino acid position 154 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.83

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.93

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.56

MetaRNN

Pathogenic

0.85

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.7

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.67

MutPred

0.36

Gain of catalytic residue at S154 (P = 0);

MVP

0.96

MPC

0.84

ClinPred

0.99

GERP RS

6.2

Varity_R

0.62

gMVP

0.52

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over