15-52205900-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12

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]

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

ACMG classification

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	c.4453T>C	p.Tyr1485His	missense_variant	37/41	ENST00000261839.12
CERNA1	NR_102751.1			downstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152218 Hom.: 0 Cov.: 33

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.: 27

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152218 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74362

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

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	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.76	N
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.17
Sift	Benign	0.081	T
Sift4G	Benign	0.11	T
Polyphen		0.60	P
Vest4		0.30
MutPred		0.73		Loss of stability (P = 0.0504);
MVP		0.43
MPC		0.18
ClinPred		0.92	D
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

Other links and lift over

dbSNP: rs1328438643; hg19: chr15-52498097;