rs2230158

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001614.5(ACTG1):c.399C>T(p.Tyr133Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,613,640 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 28 hom., cov: 33)

Exomes 𝑓: 0.014 ( 232 hom. )

Consequence

ACTG1
NM_001614.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.00900

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:

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=-0.51).

BP6

Variant 17-81511591-G-A is Benign according to our data. Variant chr17-81511591-G-A is described in ClinVar as [Benign]. Clinvar id is 128270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-81511591-G-A is described in Lovd as [Likely_benign]. Variant chr17-81511591-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.009 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0159 (2422/152338) while in subpopulation EAS AF= 0.0328 (170/5182). AF 95% confidence interval is 0.0288. There are 28 homozygotes in gnomad4. There are 1196 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2422 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTG1	NM_001614.5 link	c.399C>T	p.Tyr133Tyr	synonymous_variant	Exon 4 of 6	ENST00000573283.7	NP_001605.1	P63261
ACTG1	NM_001199954.3 link	c.399C>T	p.Tyr133Tyr	synonymous_variant	Exon 4 of 6		NP_001186883.1	P63261
ACTG1	NR_037688.3 link	n.471C>T		non_coding_transcript_exon_variant	Exon 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG1	ENST00000573283.7 link	c.399C>T	p.Tyr133Tyr	synonymous_variant	Exon 4 of 6	5	NM_001614.5	ENSP00000458435.1		P63261

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2420

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0158

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.0513

Gnomad EAS

AF:

0.0329

Gnomad SAS

AF:

0.0163

Gnomad FIN

AF:

0.00555

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.0211

GnomAD3 exomes

AF:

0.0163

AC:

4088

AN:

250184

Hom.:

AF XY:

0.0160

AC XY:

2174

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.0159

Gnomad ASJ exome

AF:

0.0486

Gnomad EAS exome

AF:

0.0303

Gnomad SAS exome

AF:

0.0169

Gnomad FIN exome

AF:

0.00624

Gnomad NFE exome

AF:

0.0131

Gnomad OTH exome

AF:

0.0194

GnomAD4 exome

AF:

0.0141

AC:

20660

AN:

1461302

Hom.:

232

Cov.:

AF XY:

0.0142

AC XY:

10339

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.0160

Gnomad4 AMR exome

AF:

0.0158

Gnomad4 ASJ exome

AF:

0.0498

Gnomad4 EAS exome

AF:

0.0225

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.00574

Gnomad4 NFE exome

AF:

0.0128

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

AF:

0.0159

AC:

2422

AN:

152338

Hom.:

Cov.:

AF XY:

0.0161

AC XY:

1196

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0159

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0513

Gnomad4 EAS

AF:

0.0328

Gnomad4 SAS

AF:

0.0161

Gnomad4 FIN

AF:

0.00555

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0164

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Feb 20, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Tyr133Tyr in Exon 04 of ACTG1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.8% (69/3736) of Afr ican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2230158). -

Nov 13, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 27, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 12, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 27, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 20

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Baraitser-winter syndrome 2

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.1

DANN

Benign

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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