12-56155117-T-C

Variant summary

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

The NM_002475.5(MYL6B):ā€‹c.265T>Cā€‹(p.Cys89Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,944 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 (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000029 ( 0 hom. )

Consequence

MYL6B
NM_002475.5 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
MYL6B (HGNC:29823): (myosin light chain 6B) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in both slow-twitch skeletal muscle and in nonmuscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

Genome browser will be placed here

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, 0.91

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYL6BNM_002475.5 linkuse as main transcriptc.265T>C p.Cys89Arg missense_variant 4/8 ENST00000695999.1 NP_002466.1 P14649A0A024RB31
MYL6BNM_001199629.2 linkuse as main transcriptc.265T>C p.Cys89Arg missense_variant 4/8 NP_001186558.1 P14649A0A024RB31
MYL6B-AS1NR_186043.1 linkuse as main transcriptn.355+2517A>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYL6BENST00000695999.1 linkuse as main transcriptc.265T>C p.Cys89Arg missense_variant 4/8 NM_002475.5 ENSP00000512320.1 P14649

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152142
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251298
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135810
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461802
Hom.:
0
Cov.:
32
AF XY:
0.0000248
AC XY:
18
AN XY:
727212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
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:
0.0000378
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152142
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsDec 18, 2023The c.265T>C (p.C89R) alteration is located in exon 4 (coding exon 3) of the MYL6B gene. This alteration results from a T to C substitution at nucleotide position 265, causing the cysteine (C) at amino acid position 89 to be replaced by an arginine (R). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.41
D
BayesDel_noAF
Pathogenic
0.37
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.47
T;T;.
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.63
.;T;T
M_CAP
Pathogenic
0.52
D
MetaRNN
Pathogenic
0.91
D;D;D
MetaSVM
Uncertain
0.69
D
MutationAssessor
Benign
1.6
L;L;.
PrimateAI
Uncertain
0.77
T
PROVEAN
Pathogenic
-7.8
D;D;D
REVEL
Pathogenic
0.85
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.84
MutPred
0.67
Gain of catalytic residue at I84 (P = 8e-04);Gain of catalytic residue at I84 (P = 8e-04);Gain of catalytic residue at I84 (P = 8e-04);
MVP
0.96
MPC
0.89
ClinPred
0.99
D
GERP RS
4.3
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.6
Varity_R
0.98
gMVP
0.93

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs774948098; hg19: chr12-56548901; API