15-52211945-T-C

Position:

• chr15-52211945-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (25518 hom., cov: 32)
  • Exomes 𝑓: 0.65 (311609 hom.)
• Consequence: MYO5C NM_018728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO5C	NM_018728.4	c.4142-61A>G		intron_variant		ENST00000261839.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO5C	ENST00000261839.12	c.4142-61A>G		intron_variant		1	NM_018728.4	P1
MYO5C	ENST00000560809.5	c.*2916-61A>G		intron_variant, NMD_transcript_variant		2
MYO5C	ENST00000559696.1	n.342-61A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82914 AN: 151924 Hom.: 25519 Cov.: 32

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

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.413

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.706

Gnomad4 OTH exome AF: 0.617

GnomAD4 genome AF: 0.545 AC: 82926 AN: 152042 Hom.: 25518 Cov.: 32 AF XY: 0.539 AC XY: 40084 AN XY: 74308

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.562

Alfa AF: 0.663 Hom.: 46845

Bravo AF: 0.518

Asia WGS AF: 0.309 AC: 1077 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.80

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: rs2278295; hg19: chr15-52504142; COSMIC: COSV55907041;