chr15-52242147-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_018728.4(MYO5C):​c.2457C>G​(p.Arg819Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.24 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 137387

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.057
DANN	Benign	0.36
PhyloP100		-1.2

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: rs3751631; hg19: chr15-52534344;