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. Variant got -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

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 -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

GnomAD3 exomes AF: 0.661 AC: 164838 AN: 249290 Hom.: 62014 AF XY: 0.672 AC XY: 90886 AN XY: 135248

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 SAS exome AF: 0.538

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

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.852

Gnomad4 EAS exome AF: 0.0258

Gnomad4 SAS exome AF: 0.555

Gnomad4 FIN exome AF: 0.837

Gnomad4 NFE exome AF: 0.810

Gnomad4 OTH exome AF: 0.704

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

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.0378

Gnomad4 SAS AF: 0.510

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.657

Alfa AF: 0.765 Hom.: 63290

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs3751631; hg19: chr15-52534344; COSMIC: COSV55906357;