rs3751631

Variant names:

• chr15-52242147-G-A
• rs3751631
• NM_018728.4:c.2457C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-52242147-G-A
• chr15-52242147-G-C
• chr15-52242147-G-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018728.4(MYO5C):​c.2457C>T​(p.Arg819Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,734 control chromosomes in the GnomAD database, including 467,352 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 0.60 (33612 hom., cov: 32)
  • Exomes 𝑓: 0.75 (433740 hom.)
• Consequence: MYO5C NM_018728.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 22 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO5C	NM_018728.4	c.2457C>T	p.Arg819Arg	synonymous_variant	Exon 20 of 41	ENST00000261839.12	NP_061198.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO5C	ENST00000261839.12	c.2457C>T	p.Arg819Arg	synonymous_variant	Exon 20 of 41	1	NM_018728.4	ENSP00000261839.7
MYO5C	ENST00000559434.1	n.1413C>T		non_coding_transcript_exon_variant	Exon 1 of 3	2
MYO5C	ENST00000558902.5	n.*2072+2209C>T		intron_variant	Intron 20 of 23	2		ENSP00000453517.1
MYO5C	ENST00000560809.5	n.*1493+2209C>T		intron_variant	Intron 19 of 37	2		ENSP00000453641.1

Frequencies

GnomAD3 genomes AF: 0.603 AC: 91634 AN: 151994 Hom.: 33621 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.0373

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.665

GnomAD2 exomes AF: 0.661 AC: 164838 AN: 249290 AF XY: 0.672

Gnomad AFR exome AF: 0.216

Gnomad AMR exome AF: 0.625

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.0343

Gnomad FIN exome AF: 0.837

Gnomad NFE exome AF: 0.811

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.751 AC: 1097950 AN: 1461622 Hom.: 433740 Cov.: 49 AF XY: 0.748 AC XY: 543988 AN XY: 727132

African (AFR) AF: 0.201 AC: 6734 AN: 33476

American (AMR) AF: 0.632 AC: 28230 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 22256 AN: 26128

East Asian (EAS) AF: 0.0258 AC: 1024 AN: 39698

South Asian (SAS) AF: 0.555 AC: 47822 AN: 86214

European-Finnish (FIN) AF: 0.837 AC: 44691 AN: 53410

Middle Eastern (MID) AF: 0.783 AC: 4514 AN: 5762

European-Non Finnish (NFE) AF: 0.810 AC: 900150 AN: 1111866

Other (OTH) AF: 0.704 AC: 42529 AN: 60382

GnomAD4 genome AF: 0.602 AC: 91626 AN: 152112 Hom.: 33612 Cov.: 32 AF XY: 0.600 AC XY: 44632 AN XY: 74354

African (AFR) AF: 0.226 AC: 9372 AN: 41470

American (AMR) AF: 0.665 AC: 10174 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2992 AN: 3468

East Asian (EAS) AF: 0.0378 AC: 196 AN: 5186

South Asian (SAS) AF: 0.510 AC: 2451 AN: 4808

European-Finnish (FIN) AF: 0.846 AC: 8955 AN: 10588

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.812 AC: 55173 AN: 67986

Other (OTH) AF: 0.657 AC: 1384 AN: 2106

Alfa AF: 0.739 Hom.: 137387

Bravo AF: 0.572

Asia WGS AF: 0.253 AC: 884 AN: 3478

EpiCase AF: 0.814

EpiControl AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs3751631; hg19: chr15-52534344; COSMIC: COSV55906357;