Variant 15-52195385-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018728.4(MYO5C):c.5068A>C(p.Lys1690Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,966 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MYO5C
NM_018728.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5C	NM_018728.4 linkuse as main transcript	c.5068A>C	p.Lys1690Gln	missense_variant	40/41	ENST00000261839.12
CERNA1	NR_102751.1 linkuse as main transcript	n.530-9504T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5C	ENST00000261839.12 linkuse as main transcript	c.5068A>C	p.Lys1690Gln	missense_variant	40/41	1	NM_018728.4	P1	Q9NQX4-1
CERNA1	ENST00000654724.1 linkuse as main transcript	n.528-9504T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248498

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458966

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

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

May 17, 2023

The c.5068A>C (p.K1690Q) alteration is located in exon 40 (coding exon 40) of the MYO5C gene. This alteration results from a A to C substitution at nucleotide position 5068, causing the lysine (K) at amino acid position 1690 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Uncertain

0.073

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.45

MetaSVM

Uncertain

0.33

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.51

Sift

Uncertain

0.024

Sift4G

Benign

0.34

Polyphen

0.97

Vest4

0.39

MutPred

0.41

Loss of ubiquitination at K1690 (P = 0.0446);

MVP

0.82

MPC

0.35

ClinPred

0.87

GERP RS

5.5

Varity_R

0.63

gMVP

0.55

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