Variant chr7-152825067-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020445.6(ACTR3B):c.896T>C(p.Val299Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ACTR3B
NM_020445.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.65

Variant links:

Genes affected

ACTR3B (HGNC:17256): (actin related protein 3B) This gene encodes a member of the actin-related proteins (ARP), which form multiprotein complexes and share 35-55% amino acid identity with conventional actin. The protein encoded by this gene may have a regulatory role in the actin cytoskeleton and induce cell-shape change and motility. Pseudogenes of this gene are located on chromosomes 2, 4, 10, 16, 22 and Y. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jul 2012]

ACTR3B links:

ACTR3B (HGNC:):

ACTR3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3B	NM_020445.6 linkuse as main transcript	c.896T>C	p.Val299Ala	missense_variant	9/12	ENST00000256001.13	NP_065178.1	Q9P1U1-1Q59GD5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACTR3B	ENST00000256001.13 linkuse as main transcript	c.896T>C	p.Val299Ala	missense_variant	9/12	1	NM_020445.6	ENSP00000256001.8	Q9P1U1-1
ACTR3B	ENST00000377776.7 linkuse as main transcript	c.896T>C	p.Val299Ala	missense_variant	9/10	1		ENSP00000367007.3	Q9P1U1-3
ACTR3B	ENST00000397282.2 linkuse as main transcript	c.632T>C	p.Val211Ala	missense_variant	8/11	2		ENSP00000380452.2	Q9P1U1-2
ACTR3B	ENST00000479402.1 linkuse as main transcript	n.4364T>C		non_coding_transcript_exon_variant	5/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461566

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727098

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:

8.99e-7

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

Jan 04, 2022

The c.896T>C (p.V299A) alteration is located in exon 9 (coding exon 9) of the ACTR3B gene. This alteration results from a T to C substitution at nucleotide position 896, causing the valine (V) at amino acid position 299 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

0.34

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;T;.

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Benign

1.8

L;L;.

PrimateAI

Pathogenic

0.83

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Pathogenic

0.80

Sift

Benign

0.044

D;D;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.87

P;P;.

Vest4

0.89

MutPred

0.57

Loss of stability (P = 0.0406);Loss of stability (P = 0.0406);.;

MVP

0.92

MPC

2.1

ClinPred

0.96

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.80

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

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