Variant 11-66546544-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001258371.3(ACTN3):c.34T>C(p.Cys12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,535,326 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 8 hom. )

Consequence

ACTN3
NM_001258371.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.21

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008911639).

BP6

Variant 11-66546544-T-C is Benign according to our data. Variant chr11-66546544-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3057224.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTN3	NM_001258371.3 linkuse as main transcript	c.34T>C	p.Cys12Arg	missense_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTN3	ENST00000502692.5 linkuse as main transcript	c.34T>C	p.Cys12Arg	missense_variant	1/21	2

Frequencies

GnomAD3 genomes

AF:

0.00155

AC:

235

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00281

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00142

AC:

182

AN:

128284

Hom.:

AF XY:

0.00149

AC XY:

105

AN XY:

70250

show subpopulations

Gnomad AFR exome

AF:

0.000657

Gnomad AMR exome

AF:

0.000698

Gnomad ASJ exome

AF:

0.000742

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000983

Gnomad FIN exome

AF:

0.00149

Gnomad NFE exome

AF:

0.00254

Gnomad OTH exome

AF:

0.00100

GnomAD4 exome

AF:

0.00186

AC:

2572

AN:

1383320

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

1256

AN XY:

682570

show subpopulations

Gnomad4 AFR exome

AF:

0.000285

Gnomad4 AMR exome

AF:

0.000644

Gnomad4 ASJ exome

AF:

0.000675

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.00215

Gnomad4 OTH exome

AF:

0.00140

GnomAD4 genome

AF:

0.00155

AC:

235

AN:

152006

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74262

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00281

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00265

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00156

AC:

ExAC

AF:

0.00108

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ACTN3-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 13, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

Cadd

Benign

2.0

Dann

Benign

0.61

DEOGEN2

Benign

0.22

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.21

MetaRNN

Benign

0.0089

PrimateAI

Benign

0.41

Vest4

0.048

MVP

0.70

GERP RS

-3.0

gMVP

0.28

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over