Genetic Variant ACTR3C:p.Glu89Gly (chr7-150289481-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001164458.2(ACTR3C):c.266A>G(p.Glu89Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000928 in 150,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000010 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29

Publications

0 publications found

Variant links:

Genes affected

ACTR3C (HGNC:37282): (actin related protein 3C) Predicted to enable ATP binding activity. Predicted to contribute to actin filament binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACTR3C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2 link	c.266A>G	p.Glu89Gly	missense_variant	Exon 4 of 8	ENST00000683684.1	NP_001157930.1	Q9C0K3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1 link	c.266A>G	p.Glu89Gly	missense_variant	Exon 4 of 8		NM_001164458.2	ENSP00000507618.1		Q9C0K3-1

Frequencies

GnomAD3 genomes

AF:

0.0000928

AC:

AN:

150788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000345

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000146

AC:

AN:

204792

AF XY:

0.0000182

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000104

AC:

AN:

1438254

Hom.:

Cov.:

AF XY:

0.0000126

AC XY:

AN XY:

712916

show subpopulations

African (AFR)

AF:

0.000373

AC:

AN:

32198

American (AMR)

AF:

0.00

AC:

AN:

42770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25274

East Asian (EAS)

AF:

0.00

AC:

AN:

38620

South Asian (SAS)

AF:

0.00

AC:

AN:

80826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52042

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.00000272

AC:

AN:

1101380

Other (OTH)

AF:

0.00

AC:

AN:

59500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.418

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000928

AC:

AN:

150788

Hom.:

Cov.:

AF XY:

0.0000544

AC XY:

AN XY:

73582

show subpopulations

African (AFR)

AF:

0.000345

AC:

AN:

40562

American (AMR)

AF:

0.00

AC:

AN:

15196

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67934

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 17, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.266A>G (p.E89G) alteration is located in exon 4 (coding exon 3) of the ACTR3C gene. This alteration results from a A to G substitution at nucleotide position 266, causing the glutamic acid (E) at amino acid position 89 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

.;D;.;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

T;T;T;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.1

.;M;.;.

PhyloP100

7.3

PROVEAN

Pathogenic

-5.6

D;D;D;D

REVEL

Uncertain

0.61

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;.

Polyphen

0.99

.;D;.;.

Vest4

0.72, 0.71

MutPred

0.31

.;Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);.;

MVP

0.93

MPC

2.2

ClinPred

0.53

GERP RS

2.2

Varity_R

0.73

gMVP

0.52

Mutation Taster

=58/42

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.30

Position offset: -31

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

Publications

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7-150289481-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over