rs1139405

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001614.5(ACTG1):c.918C>T(p.Tyr306Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,613,832 control chromosomes in the GnomAD database, including 519,901 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.76 ( 44684 hom., cov: 32)

Exomes 𝑓: 0.81 ( 475217 hom. )

Consequence

ACTG1
NM_001614.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

ACTG1 (HGNC:144): (actin gamma 1) Actins are highly conserved proteins that are involved in various types of cell motility and in maintenance of the cytoskeleton. Three main groups of actin isoforms have been identified in vertebrate animals: alpha, beta, and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. Actin gamma 1, encoded by this gene, is a cytoplasmic actin found in all cell types. Mutations in this gene are associated with DFNA20/26, a subtype of autosomal dominant non-syndromic sensorineural progressive hearing loss and also with Baraitser-Winter syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2017]

ACTG1 links:

ACTG1 (HGNC:):

ACTG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-81510993-G-A is Benign according to our data. Variant chr17-81510993-G-A is described in ClinVar as [Benign]. Clinvar id is 44150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81510993-G-A is described in Lovd as [Likely_benign]. Variant chr17-81510993-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.79 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTG1	NM_001614.5 linkuse as main transcript	c.918C>T	p.Tyr306Tyr	synonymous_variant	5/6	ENST00000573283.7	NP_001605.1	P63261
ACTG1	NM_001199954.3 linkuse as main transcript	c.918C>T	p.Tyr306Tyr	synonymous_variant	5/6		NP_001186883.1	P63261
ACTG1	NR_037688.3 linkuse as main transcript	n.990C>T		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTG1	ENST00000573283.7 linkuse as main transcript	c.918C>T	p.Tyr306Tyr	synonymous_variant	5/6	5	NM_001614.5	ENSP00000458435.1		P63261

Frequencies

GnomAD3 genomes

AF:

0.762

AC:

115797

AN:

151986

Hom.:

44671

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.871

Gnomad AMR

AF:

0.739

Gnomad ASJ

AF:

0.814

Gnomad EAS

AF:

0.858

Gnomad SAS

AF:

0.792

Gnomad FIN

AF:

0.835

Gnomad MID

AF:

0.737

Gnomad NFE

AF:

0.821

Gnomad OTH

AF:

0.777

GnomAD3 exomes

AF:

0.788

AC:

198064

AN:

251344

Hom.:

78611

AF XY:

0.793

AC XY:

107764

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.629

Gnomad AMR exome

AF:

0.690

Gnomad ASJ exome

AF:

0.804

Gnomad EAS exome

AF:

0.877

Gnomad SAS exome

AF:

0.784

Gnomad FIN exome

AF:

0.837

Gnomad NFE exome

AF:

0.816

Gnomad OTH exome

AF:

0.800

GnomAD4 exome

AF:

0.805

AC:

1177071

AN:

1461728

Hom.:

475217

Cov.:

AF XY:

0.806

AC XY:

585879

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.626

Gnomad4 AMR exome

AF:

0.698

Gnomad4 ASJ exome

AF:

0.810

Gnomad4 EAS exome

AF:

0.822

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.835

Gnomad4 NFE exome

AF:

0.815

Gnomad4 OTH exome

AF:

0.795

GnomAD4 genome

AF:

0.762

AC:

115848

AN:

152104

Hom.:

44684

Cov.:

AF XY:

0.763

AC XY:

56731

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.631

Gnomad4 AMR

AF:

0.739

Gnomad4 ASJ

AF:

0.814

Gnomad4 EAS

AF:

0.858

Gnomad4 SAS

AF:

0.793

Gnomad4 FIN

AF:

0.835

Gnomad4 NFE

AF:

0.821

Gnomad4 OTH

AF:

0.778

Alfa

AF:

0.790

Hom.:

22027

Bravo

AF:

0.748

Asia WGS

AF:

0.776

AC:

2697

AN:

3478

EpiCase

AF:

0.813

EpiControl

AF:

0.811

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Tyr306Tyr in Exon 05 of ACTG1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 35.7% (1333/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1139405). -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 15, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Autosomal dominant nonsyndromic hearing loss 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Autosomal dominant nonsyndromic hearing loss 20;C3281235:Baraitser-winter syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Baraitser-winter syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.1

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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