NM_018728.4:c.28-81G>A

Variant names:

• chr15-52282973-C-T
• rs3751624
• NM_018728.4:c.28-81G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018728.4(MYO5C):​c.28-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 902,972 control chromosomes in the GnomAD database, including 14,742 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 0.20 (3287 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11455 hom.)
• Consequence: MYO5C NM_018728.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 10 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018728.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5C	NM_018728.4	MANE Select	c.28-81G>A		intron	N/A	NP_061198.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5C	ENST00000261839.12	TSL:1 MANE Select	c.28-81G>A		intron	N/A	ENSP00000261839.7
	MYO5C	ENST00000559459.5	TSL:1	n.28-81G>A		intron	N/A	ENSP00000454064.1
	MYO5C	ENST00000558479.1	TSL:3	c.-286-89G>A		intron	N/A	ENSP00000453514.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29803 AN: 152052 Hom.: 3282 Cov.: 32

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.168 AC: 125799 AN: 750802 Hom.: 11455 AF XY: 0.170 AC XY: 67140 AN XY: 395722

African (AFR) AF: 0.291 AC: 5765 AN: 19796

American (AMR) AF: 0.131 AC: 4780 AN: 36464

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 5655 AN: 21136

East Asian (EAS) AF: 0.0633 AC: 2203 AN: 34810

South Asian (SAS) AF: 0.205 AC: 13832 AN: 67466

European-Finnish (FIN) AF: 0.103 AC: 5107 AN: 49452

Middle Eastern (MID) AF: 0.229 AC: 1013 AN: 4430

European-Non Finnish (NFE) AF: 0.168 AC: 80773 AN: 480462

Other (OTH) AF: 0.181 AC: 6671 AN: 36786

GnomAD4 genome AF: 0.196 AC: 29831 AN: 152170 Hom.: 3287 Cov.: 32 AF XY: 0.191 AC XY: 14240 AN XY: 74418

African (AFR) AF: 0.294 AC: 12196 AN: 41500

American (AMR) AF: 0.158 AC: 2417 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 950 AN: 3472

East Asian (EAS) AF: 0.0908 AC: 469 AN: 5166

South Asian (SAS) AF: 0.215 AC: 1037 AN: 4824

European-Finnish (FIN) AF: 0.0959 AC: 1017 AN: 10604

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11053 AN: 67994

Other (OTH) AF: 0.196 AC: 413 AN: 2110

Alfa AF: 0.175 Hom.: 10409

Bravo AF: 0.203

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.80
PhyloP100		-0.78
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: rs3751624; hg19: chr15-52575170; COSMIC: COSV55903965;