Genetic Variant MYO5C:c.4142-61A>G (chr15-52211945-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018728.4(MYO5C):c.4142-61A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,556,024 control chromosomes in the GnomAD database, including 337,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.55 ( 25518 hom., cov: 32)

Exomes 𝑓: 0.65 ( 311609 hom. )

Consequence

MYO5C
NM_018728.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.184

Publications

18 publications found

Variant links:

Genes affected

MYO5C (HGNC:7604): (myosin VC) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MYO5C links:

CERNA1 (HGNC:52664): (competing endogenous lncRNA 1 for miR-4707-5p and miR-4767)

CERNA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5C	NM_018728.4	MANE Select	c.4142-61A>G		intron	N/A	NP_061198.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYO5C	ENST00000261839.12	TSL:1 MANE Select	c.4142-61A>G	intron	N/A	ENSP00000261839.7
MYO5C	ENST00000930074.1		c.4109-61A>G	intron	N/A	ENSP00000600133.1
MYO5C	ENST00000930075.1		c.4142-61A>G	intron	N/A	ENSP00000600134.1

Frequencies

GnomAD3 genomes

AF:

0.546

AC:

82914

AN:

151924

Hom.:

25519

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.708

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.709

Gnomad OTH

AF:

0.565

GnomAD4 exome

AF:

0.653

AC:

917168

AN:

1403982

Hom.:

311609

AF XY:

0.649

AC XY:

450540

AN XY:

694452

show subpopulations

African (AFR)

AF:

0.274

AC:

8737

AN:

31922

American (AMR)

AF:

0.402

AC:

15673

AN:

38940

Ashkenazi Jewish (ASJ)

AF:

0.709

AC:

16563

AN:

23376

East Asian (EAS)

AF:

0.222

AC:

8697

AN:

39100

South Asian (SAS)

AF:

0.413

AC:

32687

AN:

79182

European-Finnish (FIN)

AF:

0.689

AC:

34380

AN:

49868

Middle Eastern (MID)

AF:

0.635

AC:

2920

AN:

4602

European-Non Finnish (NFE)

AF:

0.706

AC:

761816

AN:

1079170

Other (OTH)

AF:

0.617

AC:

35695

AN:

57822

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14454

28909

43363

57818

72272

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19136

38272

57408

76544

95680

<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:

0.545

AC:

82926

AN:

152042

Hom.:

25518

Cov.:

AF XY:

0.539

AC XY:

40084

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.294

AC:

12170

AN:

41450

American (AMR)

AF:

0.506

AC:

7742

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.708

AC:

2458

AN:

3472

East Asian (EAS)

AF:

0.231

AC:

1193

AN:

5162

South Asian (SAS)

AF:

0.397

AC:

1912

AN:

4818

European-Finnish (FIN)

AF:

0.690

AC:

7288

AN:

10560

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.709

AC:

48231

AN:

67982

Other (OTH)

AF:

0.562

AC:

1183

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1659

3318

4978

6637

8296

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

686

1372

2058

2744

3430

<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:

0.625

Hom.:

61521

Bravo

AF:

0.518

Asia WGS

AF:

0.309

AC:

1077

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

7.3

(source)

DANN

Benign

0.80

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over