7-152823439-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_020445.6(ACTR3B):c.782C>T(p.Ala261Val) variant causes a missense change. The variant allele was found at a frequency of 0.000478 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

ACTR3B
NM_020445.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.90

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant where missense usually causes diseases, ACTR3B

BP4

Computational evidence support a benign effect (MetaRNN=0.021694511).

BS2

High AC in GnomAd at 75 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR3B	NM_020445.6 linkuse as main transcript	c.782C>T	p.Ala261Val	missense_variant	8/12	ENST00000256001.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR3B	ENST00000256001.13 linkuse as main transcript	c.782C>T	p.Ala261Val	missense_variant	8/12	1	NM_020445.6	P1	Q9P1U1-1
ACTR3B	ENST00000377776.7 linkuse as main transcript	c.782C>T	p.Ala261Val	missense_variant	8/10	1			Q9P1U1-3
ACTR3B	ENST00000397282.2 linkuse as main transcript	c.518C>T	p.Ala173Val	missense_variant	7/11	2			Q9P1U1-2
ACTR3B	ENST00000479402.1 linkuse as main transcript	n.4250C>T		non_coding_transcript_exon_variant	4/8	2

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000577

AC:

145

AN:

251470

Hom.:

AF XY:

0.000581

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000782

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000476

AC:

696

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000466

AC XY:

339

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00287

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000468

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000492

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000833

Hom.:

Bravo

AF:

0.000604

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000527

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

Oct 26, 2022

The c.782C>T (p.A261V) alteration is located in exon 8 (coding exon 8) of the ACTR3B gene. This alteration results from a C to T substitution at nucleotide position 782, causing the alanine (A) at amino acid position 261 to be replaced by a valine (V). 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

0.11

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.022

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.12

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.26

T;T;T

Polyphen

0.12

B;B;.

Vest4

0.45

MVP

0.21

MPC

0.94

ClinPred

0.019

GERP RS

3.9

Varity_R

0.13

gMVP

0.65

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