Variant 7-150289479-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001164458.2(ACTR3C):c.268C>G(p.Gln90Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000176 in 1,588,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.06

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:

ACTR3C (HGNC:):

ACTR3C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3041855).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3C	NM_001164458.2 linkuse as main transcript	c.268C>G	p.Gln90Glu	missense_variant	4/8	ENST00000683684.1	NP_001157930.1	Q9C0K3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1 linkuse as main transcript	c.268C>G	p.Gln90Glu	missense_variant	4/8		NM_001164458.2	ENSP00000507618.1		Q9C0K3-1

Frequencies

GnomAD3 genomes

AF:

0.00000663

AC:

AN:

150722

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000535

AC:

AN:

205610

Hom.:

AF XY:

0.0000636

AC XY:

AN XY:

110110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000645

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000355

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000190

GnomAD4 exome

AF:

0.0000188

AC:

AN:

1437548

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

712402

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000117

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000260

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.00000663

AC:

AN:

150722

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73538

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.268C>G (p.Q90E) alteration is located in exon 4 (coding exon 3) of the ACTR3C gene. This alteration results from a C to G substitution at nucleotide position 268, causing the glutamine (Q) at amino acid position 90 to be replaced by a glutamic acid (E). 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

Benign

0.12

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

D;D;D;D

M_CAP

Benign

0.0094

MetaRNN

Benign

0.30

T;T;T;T

MetaSVM

Uncertain

0.40

MutationAssessor

Benign

0.73

.;N;.;.

PROVEAN

Benign

-0.12

N;N;N;N

REVEL

Uncertain

0.44

Sift

Benign

0.73

T;T;T;T

Sift4G

Benign

0.40

T;T;T;.

Polyphen

1.0

.;D;.;.

Vest4

0.68, 0.69

MutPred

0.61

.;Gain of disorder (P = 0.0927);Gain of disorder (P = 0.0927);.;

MVP

0.81

MPC

2.0

ClinPred

0.21

GERP RS

2.2

Varity_R

0.14

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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