chr11-66559110-T-G

Variant names:

• chr11-66559110-T-G
• rs2275998
• NM_001104.4:c.1277-126T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001104.4(ACTN3):​c.1277-126T>G variant causes a intron 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 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685
• 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]

ENSG00000250105 (HGNC:58248):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.1277-126T>G		intron	N/A	NP_001095.2
	ACTN3	NM_001258371.3		c.1406-126T>G		intron	N/A	NP_001245300.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTN3	ENST00000513398.2	TSL:1 MANE Select	c.1277-126T>G		intron	N/A	ENSP00000426797.1
	ENSG00000250105	ENST00000504911.1	TSL:3	n.336A>C		non_coding_transcript_exon	Exon 2 of 2
	ACTN3	ENST00000502692.5	TSL:2	c.1406-126T>G		intron	N/A	ENSP00000422007.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 12

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.48
PhyloP100		-0.69

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: rs2275998; hg19: chr11-66326581;