Variant chr7-152852193-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020445.6(ACTR3B):c.1019A>G(p.Lys340Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ACTR3B
NM_020445.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.79

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR3B	NM_020445.6 linkuse as main transcript	c.1019A>G	p.Lys340Arg	missense_variant	10/12	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.1019A>G	p.Lys340Arg	missense_variant	10/12	1	NM_020445.6	ENSP00000256001.8	Q9P1U1-1
ACTR3B	ENST00000377776.7 linkuse as main transcript	c.952-2265A>G		intron_variant		1		ENSP00000367007.3	Q9P1U1-3
ACTR3B	ENST00000397282.2 linkuse as main transcript	c.755A>G	p.Lys252Arg	missense_variant	9/11	2		ENSP00000380452.2	Q9P1U1-2
ACTR3B	ENST00000479402.1 linkuse as main transcript	n.4487A>G		non_coding_transcript_exon_variant	6/8	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251450

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00000684

AC:

AN:

1461372

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726998

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000810

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

Nov 26, 2024

The c.1019A>G (p.K340R) alteration is located in exon 10 (coding exon 10) of the ACTR3B gene. This alteration results from a A to G substitution at nucleotide position 1019, causing the lysine (K) at amino acid position 340 to be replaced by an arginine (R). 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

0.086

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

T;.

Eigen

Benign

-0.089

Eigen_PC

Benign

-0.0081

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.47

T;T

MetaSVM

Uncertain

0.30

MutationAssessor

Benign

1.7

L;.

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.0

N;N

REVEL

Uncertain

0.57

Sift

Benign

0.22

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.015

B;.

Vest4

0.65

MutPred

0.29

Gain of disorder (P = 0.1129);.;

MVP

0.89

MPC

0.84

ClinPred

0.52

GERP RS

5.1

Varity_R

0.22

gMVP

0.73

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