Variant 2-113951528-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005721.5(ACTR3):c.908T>C(p.Val303Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ACTR3
NM_005721.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

Variant links:

Genes affected

ACTR3 (HGNC:170): (actin related protein 3) The specific function of this gene has not yet been determined; however, the protein it encodes is known to be a major constituent of the ARP2/3 complex. This complex is located at the cell surface and is essential to cell shape and motility through lamellipodial actin assembly and protrusion. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Mar 2013]

ACTR3 links:

ACTR3 (HGNC:):

ACTR3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3	NM_005721.5 linkuse as main transcript	c.908T>C	p.Val303Ala	missense_variant	9/12	ENST00000263238.7	NP_005712.1	P61158A0A024RAI1
ACTR3	NM_001277140.1 linkuse as main transcript	c.755T>C	p.Val252Ala	missense_variant	9/12		NP_001264069.1	B4DXW1
ACTR3	NR_102318.1 linkuse as main transcript	n.1129T>C		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACTR3	ENST00000263238.7 linkuse as main transcript	c.908T>C	p.Val303Ala	missense_variant	9/12	1	NM_005721.5	ENSP00000263238.2	P61158
ACTR3	ENST00000535589.3 linkuse as main transcript	c.755T>C	p.Val252Ala	missense_variant	9/12	2		ENSP00000444987.1	B4DXW1
ACTR3	ENST00000478928.1 linkuse as main transcript	n.705T>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 30, 2023

The c.908T>C (p.V303A) alteration is located in exon 9 (coding exon 9) of the ACTR3 gene. This alteration results from a T to C substitution at nucleotide position 908, causing the valine (V) at amino acid position 303 to be replaced by an alanine (A). 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

0.54

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

T;.

Eigen

Benign

0.052

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D

M_CAP

Uncertain

0.092

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Uncertain

0.085

MutationAssessor

Benign

0.63

N;.

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.64

Sift

Benign

0.34

T;T

Sift4G

Benign

0.50

T;T

Polyphen

0.057

B;.

Vest4

0.72

MutPred

0.52

Loss of stability (P = 0.0216);.;

MVP

0.96

MPC

1.6

ClinPred

0.94

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.51

gMVP

0.80

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over