Genetic Variant MYO5C:c.28-81G>A (chr15-52282973-C-T) – 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.28-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 902,972 control chromosomes in the GnomAD database, including 14,742 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3287 hom., cov: 32)

Exomes 𝑓: 0.17 ( 11455 hom. )

Consequence

MYO5C
NM_018728.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.776

Publications

10 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:

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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=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MYO5C	NM_018728.4 link	c.28-81G>A	intron_variant	Intron 1 of 40	ENST00000261839.12	NP_061198.2
MYO5C	XM_011521781.4 link	c.28-81G>A	intron_variant	Intron 1 of 40		XP_011520083.1
MYO5C	XM_017022408.3 link	c.28-81G>A	intron_variant	Intron 1 of 39		XP_016877897.1
MYO5C	XM_047432845.1 link	c.28-81G>A	intron_variant	Intron 1 of 39		XP_047288801.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5C	ENST00000261839.12 link	c.28-81G>A		intron_variant	Intron 1 of 40	1	NM_018728.4	ENSP00000261839.7

Frequencies

GnomAD3 genomes

AF:

0.196

AC:

29803

AN:

152052

Hom.:

3282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.274

Gnomad EAS

AF:

0.0906

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.0959

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.194

GnomAD4 exome

AF:

0.168

AC:

125799

AN:

750802

Hom.:

11455

AF XY:

0.170

AC XY:

67140

AN XY:

395722

show subpopulations

African (AFR)

AF:

0.291

AC:

5765

AN:

19796

American (AMR)

AF:

0.131

AC:

4780

AN:

36464

Ashkenazi Jewish (ASJ)

AF:

0.268

AC:

5655

AN:

21136

East Asian (EAS)

AF:

0.0633

AC:

2203

AN:

34810

South Asian (SAS)

AF:

0.205

AC:

13832

AN:

67466

European-Finnish (FIN)

AF:

0.103

AC:

5107

AN:

49452

Middle Eastern (MID)

AF:

0.229

AC:

1013

AN:

4430

European-Non Finnish (NFE)

AF:

0.168

AC:

80773

AN:

480462

Other (OTH)

AF:

0.181

AC:

6671

AN:

36786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5282

10564

15846

21128

26410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1750

3500

5250

7000

8750

<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:

0.196

AC:

29831

AN:

152170

Hom.:

3287

Cov.:

AF XY:

0.191

AC XY:

14240

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.294

AC:

12196

AN:

41500

American (AMR)

AF:

0.158

AC:

2417

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

950

AN:

3472

East Asian (EAS)

AF:

0.0908

AC:

469

AN:

5166

South Asian (SAS)

AF:

0.215

AC:

1037

AN:

4824

European-Finnish (FIN)

AF:

0.0959

AC:

1017

AN:

10604

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11053

AN:

67994

Other (OTH)

AF:

0.196

AC:

413

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1206

2412

3619

4825

6031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.175

Hom.:

10409

Bravo

AF:

0.203

Asia WGS

AF:

0.160

AC:

557

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.80

PhyloP100

-0.78

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over