Variant 12-80718416-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005593.3(MYF5):c.560G>C(p.Cys187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,613,144 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MYF5
NM_005593.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0420

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22289217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYF5	NM_005593.3 linkuse as main transcript	c.560G>C	p.Cys187Ser	missense_variant	2/3	ENST00000228644.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYF5	ENST00000228644.4 linkuse as main transcript	c.560G>C	p.Cys187Ser	missense_variant	2/3	1	NM_005593.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251466

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000144

AC:

AN:

1460958

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000171

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00191

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.000234

ExAC

AF:

0.00000824

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

Jan 10, 2022

The c.560G>C (p.C187S) alteration is located in exon 2 (coding exon 2) of the MYF5 gene. This alteration results from a G to C substitution at nucleotide position 560, causing the cysteine (C) at amino acid position 187 to be replaced by a serine (S). 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

Benign

0.15

BayesDel_addAF

Benign

-0.066

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Benign

0.88

DEOGEN2

Benign

0.27

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.49

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.22

MetaSVM

Pathogenic

0.85

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.94

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.47

Sift

Benign

0.44

Sift4G

Benign

0.60

Polyphen

0.99

Vest4

0.14

MutPred

0.33

Gain of disorder (P = 0.0227);

MVP

0.84

MPC

0.22

ClinPred

0.23

GERP RS

3.2

Varity_R

0.10

gMVP

0.29

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

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