15-52211945-T-C

Variant names:

• chr15-52211945-T-C
• rs2278295
• NM_018728.4:c.4142-61A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYO5C	NM_018728.4	c.4142-61A>G		intron_variant	Intron 34 of 40	ENST00000261839.12	NP_061198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5C	ENST00000261839.12	c.4142-61A>G		intron_variant	Intron 34 of 40	1	NM_018728.4	ENSP00000261839.7
MYO5C	ENST00000559696.1	n.342-61A>G		intron_variant	Intron 1 of 4	5
MYO5C	ENST00000560809.5	n.*2916-61A>G		intron_variant	Intron 31 of 37	2		ENSP00000453641.1
CERNA1	ENST00000821889.1	n.176+5640T>C		intron_variant	Intron 2 of 3

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

African (AFR) AF: 0.274 AC: 8737 AN: 31922

American (AMR) AF: 0.402 AC: 15673 AN: 38940

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 16563 AN: 23376

East Asian (EAS) AF: 0.222 AC: 8697 AN: 39100

South Asian (SAS) AF: 0.413 AC: 32687 AN: 79182

European-Finnish (FIN) AF: 0.689 AC: 34380 AN: 49868

Middle Eastern (MID) AF: 0.635 AC: 2920 AN: 4602

European-Non Finnish (NFE) AF: 0.706 AC: 761816 AN: 1079170

Other (OTH) AF: 0.617 AC: 35695 AN: 57822

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

African (AFR) AF: 0.294 AC: 12170 AN: 41450

American (AMR) AF: 0.506 AC: 7742 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2458 AN: 3472

East Asian (EAS) AF: 0.231 AC: 1193 AN: 5162

South Asian (SAS) AF: 0.397 AC: 1912 AN: 4818

European-Finnish (FIN) AF: 0.690 AC: 7288 AN: 10560

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48231 AN: 67982

Other (OTH) AF: 0.562 AC: 1183 AN: 2106

Alfa AF: 0.625 Hom.: 61521

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
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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