Variant chr15-52205900-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_018728.4(MYO5C):c.4453T>C(p.Tyr1485His) variant causes a missense change. The variant allele was found at a frequency of 0.0000328 in 152,218 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 0.000033 ( 0 hom., cov: 33)

Consequence

MYO5C
NM_018728.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.12

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38762254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5C	NM_018728.4 linkuse as main transcript	c.4453T>C	p.Tyr1485His	missense_variant	37/41	ENST00000261839.12
CERNA1	NR_102751.1 linkuse as main transcript			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5C	ENST00000261839.12 linkuse as main transcript	c.4453T>C	p.Tyr1485His	missense_variant	37/41	1	NM_018728.4	P1	Q9NQX4-1
CERNA1	ENST00000654724.1 linkuse as main transcript	n.1539A>G		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152218

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Mar 07, 2024

The c.4453T>C (p.Y1485H) alteration is located in exon 37 (coding exon 37) of the MYO5C gene. This alteration results from a T to C substitution at nucleotide position 4453, causing the tyrosine (Y) at amino acid position 1485 to be replaced by a histidine (H). 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

0.23

BayesDel_addAF

Benign

-0.098

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.0053

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.76

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.17

Sift

Benign

0.081

Sift4G

Benign

0.11

Polyphen

0.60

Vest4

0.30

MutPred

0.73

Loss of stability (P = 0.0504);

MVP

0.43

MPC

0.18

ClinPred

0.92

GERP RS

5.2

Varity_R

0.38

gMVP

0.58

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

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