Variant 12-56157480-C-G 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_002475.5(MYL6B):c.533C>G(p.Thr178Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000149 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

MYL6B
NM_002475.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28

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]

MYL6B links:

MYL6B-AS1 (HGNC:55472): (MYL6B antisense RNA 1)

MYL6B-AS1 links:

Genome browser will be placed here

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=0.17572919).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL6B	NM_002475.5 linkuse as main transcript	c.533C>G	p.Thr178Ser	missense_variant	6/8	ENST00000695999.1	NP_002466.1
MYL6B	NM_001199629.2 linkuse as main transcript	c.533C>G	p.Thr178Ser	missense_variant	6/8		NP_001186558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL6B	ENST00000695999.1 linkuse as main transcript	c.533C>G	p.Thr178Ser	missense_variant	6/8		NM_002475.5	ENSP00000512320	P1
MYL6B-AS1	ENST00000548731.1 linkuse as main transcript	n.350+154G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000987

AC:

AN:

152014

Hom.:

Cov.:

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:

0.000206

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000135

AC:

AN:

251252

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

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:

0.000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000154

AC:

225

AN:

1461828

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

112

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000190

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000987

AC:

AN:

152014

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74244

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:

0.000206

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.000121

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

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

Oct 22, 2021

The c.533C>G (p.T178S) alteration is located in exon 6 (coding exon 5) of the MYL6B gene. This alteration results from a C to G substitution at nucleotide position 533, causing the threonine (T) at amino acid position 178 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

0.11

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;T;.

Eigen

Benign

0.070

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.70

.;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.18

N;N;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.4

N;N;N

REVEL

Uncertain

0.38

Sift

Benign

0.29

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.34

B;B;.

Vest4

0.32

MutPred

0.33

Gain of ubiquitination at K176 (P = 0.0719);Gain of ubiquitination at K176 (P = 0.0719);.;

MVP

0.82

MPC

0.15

ClinPred

0.18

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.22

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