Genetic Variant NM_002477.2:c.323C>T (chr4-680539-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002477.2(MYL5):c.323C>T(p.Ala108Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000399 in 1,613,464 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A108T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 2 hom. )

Consequence

MYL5
NM_002477.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

Publications

5 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 gene

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.323C>T	p.Ala108Val	missense	Exon 7 of 9	NP_002468.1	Q02045-1
MYL5	NM_001395441.1		c.323C>T	p.Ala108Val	missense	Exon 7 of 9	NP_001382370.1	Q02045-1
MYL5	NM_001395442.1		c.323C>T	p.Ala108Val	missense	Exon 7 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.323C>T	p.Ala108Val	missense	Exon 7 of 9	ENSP00000383023.2	Q02045-1
MYL5	ENST00000511290.5	TSL:1	c.200C>T	p.Ala67Val	missense	Exon 5 of 7	ENSP00000425162.1	Q02045-2
MYL5	ENST00000894694.1		c.323C>T	p.Ala108Val	missense	Exon 7 of 9	ENSP00000564753.1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000153

AC:

AN:

249026

AF XY:

0.000140

show subpopulations

Gnomad AFR exome

AF:

0.0000647

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000222

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000423

AC:

618

AN:

1461278

Hom.:

Cov.:

AF XY:

0.000409

AC XY:

297

AN XY:

726944

show subpopulations

African (AFR)

AF:

0.0000597

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000499

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.000170

AC:

AN:

52930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000496

AC:

551

AN:

1111928

Other (OTH)

AF:

0.000215

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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

AF:

0.000171

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000207

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.523

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.000141

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.10

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Benign

0.11

Eigen_PC

Benign

-0.0053

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.49

MutationAssessor

Pathogenic

3.2

PhyloP100

3.1

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.8

REVEL

Uncertain

0.45

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.020

Polyphen

0.90

Vest4

0.70

MVP

0.61

MPC

0.25

ClinPred

0.73

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.54

Mutation Taster

=94/6

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over