NM_001104.4:c.1729C>A

Variant names:

• chr11-66560624-C-A
• rs1815739
• NM_001104.4:c.1729C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001104.4(ACTN3):​c.1729C>A​(p.Arg577Arg) 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: ACTN3 NM_001104.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.34
• Publications: 552 publications found

Genes affected

ACTN3 (HGNC:165): (actinin alpha 3) This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the coding allele. The non-functional allele of this gene is associated with elite athlete status. [provided by RefSeq, Feb 2014]

ACTN3-AS1 (HGNC:58248):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.09).
• BP7: Synonymous conserved (PhyloP=1.34 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001104.4. 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
	ACTN3	NM_001104.4	MANE Select	c.1729C>A	p.Arg577Arg	synonymous	Exon 15 of 21	NP_001095.2
	ACTN3	NM_001258371.3		c.1858C>A	p.Arg620Arg	synonymous	Exon 15 of 21	NP_001245300.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN3	ENST00000513398.2	TSL:1 MANE Select	c.1729C>A	p.Arg577Arg	synonymous	Exon 15 of 21	ENSP00000426797.1
	ACTN3	ENST00000502692.5	TSL:2	c.1858C>A	p.Arg620Arg	synonymous	Exon 15 of 21	ENSP00000422007.1
	ACTN3	ENST00000968415.1		c.1738C>A	p.Arg580Arg	synonymous	Exon 15 of 21	ENSP00000638474.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.090
CADD	Benign	9.5
PhyloP100		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1815739; hg19: chr11-66328095;