Genetic Variant NM_002477.2:c.34G>A (chr4-678688-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002477.2(MYL5):c.34G>A(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000685 in 1,458,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

MYL5
NM_002477.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

Publications

0 publications found

Variant links:

Genes affected

MYL5 (HGNC:7586): (myosin light chain 5) This gene encodes one of the myosin light chains, a component of the hexameric ATPase cellular motor protein myosin. Myosin is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene product, one of the regulatory light chains, is expressed in fetal muscle and in adult retina, cerebellum, and basal ganglia. [provided by RefSeq, Jul 2008]

MYL5 links:

SLC49A3 (HGNC:26177): (solute carrier family 49 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC49A3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14054552).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002477.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYL5	NM_002477.2	MANE Select	c.34G>A	p.Gly12Ser	missense	Exon 4 of 9	NP_002468.1	Q02045-1
MYL5	NM_001395441.1		c.34G>A	p.Gly12Ser	missense	Exon 4 of 9	NP_001382370.1	Q02045-1
MYL5	NM_001395442.1		c.34G>A	p.Gly12Ser	missense	Exon 4 of 9	NP_001382371.1	Q02045-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYL5	ENST00000400159.7	TSL:1 MANE Select	c.34G>A	p.Gly12Ser	missense	Exon 4 of 9	ENSP00000383023.2	Q02045-1
MYL5	ENST00000511290.5	TSL:1	c.-90G>A		5_prime_UTR	Exon 2 of 7	ENSP00000425162.1	Q02045-2
MYL5	ENST00000894694.1		c.34G>A	p.Gly12Ser	missense	Exon 4 of 9	ENSP00000564753.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000208

AC:

AN:

240562

AF XY:

0.0000305

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000228

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1458806

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33446

American (AMR)

AF:

0.00

AC:

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.0000757

AC:

AN:

39616

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85766

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111094

Other (OTH)

AF:

0.0000664

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000166

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.79

M_CAP

Benign

0.047

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.63

PhyloP100

2.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.0

REVEL

Benign

0.13

Sift

Benign

0.12

Sift4G

Benign

0.12

Polyphen

0.58

Vest4

0.26

MutPred

0.20

Gain of phosphorylation at G12 (P = 0.0134)

MVP

0.53

MPC

0.22

ClinPred

0.15

GERP RS

2.8

PromoterAI

0.017

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.069

gMVP

0.29

Mutation Taster

=291/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over