Variant 7-150293323-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001164458.2(ACTR3C):c.142G>A(p.Val48Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000151 in 1,586,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.30

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05090311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3C	NM_001164458.2 linkuse as main transcript	c.142G>A	p.Val48Ile	missense_variant	3/8	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.142G>A	p.Val48Ile	missense_variant	3/8		NM_001164458.2	ENSP00000507618.1		Q9C0K3-1

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000730

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000193

AC:

AN:

206904

Hom.:

AF XY:

0.0000273

AC XY:

AN XY:

109780

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.0000661

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1434826

Hom.:

Cov.:

AF XY:

0.00000985

AC XY:

AN XY:

710788

show subpopulations

Gnomad4 AFR exome

AF:

0.000211

Gnomad4 AMR exome

AF:

0.000168

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000274

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151454

Hom.:

Cov.:

AF XY:

0.0000541

AC XY:

AN XY:

73884

show subpopulations

Gnomad4 AFR

AF:

0.0000730

Gnomad4 AMR

AF:

0.000197

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:

0.0000248

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

Sep 08, 2024

The c.142G>A (p.V48I) alteration is located in exon 3 (coding exon 2) of the ACTR3C gene. This alteration results from a G to A substitution at nucleotide position 142, causing the valine (V) at amino acid position 48 to be replaced by an isoleucine (I). 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

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.24

T;.;.;.

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

D;D;D;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.051

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.64

N;.;.;.

PROVEAN

Benign

-0.53

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.33

T;T;T;T

Sift4G

Benign

0.53

T;T;.;T

Polyphen

0.0040

B;.;.;.

Vest4

0.25

MutPred

0.51

Loss of glycosylation at T46 (P = 0.1195);Loss of glycosylation at T46 (P = 0.1195);.;Loss of glycosylation at T46 (P = 0.1195);

MVP

0.13

MPC

1.6

ClinPred

0.16

GERP RS

0.80

Varity_R

0.028

gMVP

0.32

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