11-66546753-C-T

Variant names:

• chr11-66546753-C-T
• rs150880895
• NM_001258371.3:c.243C>T

Variant summary

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

The NM_001258371.3(ACTN3):​c.243C>T​(p.Pro81Pro) 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. Synonymous variant affecting the same amino acid position (i.e. P81P) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ACTN3 NM_001258371.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282
• Publications: 0 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]

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=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.282 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTN3	NM_001258371.3	c.243C>T	p.Pro81Pro	synonymous_variant	Exon 1 of 21		NP_001245300.2
ACTN3	NM_001104.4	c.-185C>T		upstream_gene_variant		ENST00000513398.2	NP_001095.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTN3	ENST00000502692.5	c.243C>T	p.Pro81Pro	synonymous_variant	Exon 1 of 21	2		ENSP00000422007.1
ACTN3	ENST00000513398.2	c.-185C>T		upstream_gene_variant		1	NM_001104.4	ENSP00000426797.1
ACTN3	ENST00000511191.1	n.-185C>T		upstream_gene_variant		5		ENSP00000426236.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.75
PhyloP100		-0.28
PromoterAI		0.0012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs150880895; hg19: chr11-66314224;