Variant 3-53871370-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022899.5(ACTR8):c.1429C>G(p.Gln477Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ACTR8
NM_022899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.38

Variant links:

Genes affected

ACTR8 (HGNC:14672): (actin related protein 8) Predicted to enable ATP binding activity. Predicted to be involved in chromatin remodeling; double-strand break repair; and regulation of transcription, DNA-templated. Located in centrosome and nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACTR8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26178846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ACTR8	NM_022899.5 linkuse as main transcript	c.1429C>G	p.Gln477Glu	missense_variant	11/13	ENST00000335754.8	NP_075050.3
ACTR8	NM_001410774.1 linkuse as main transcript	c.1096C>G	p.Gln366Glu	missense_variant	11/13		NP_001397703.1
ACTR8	XM_005265587.6 linkuse as main transcript	c.1429C>G	p.Gln477Glu	missense_variant	11/14		XP_005265644.1
ACTR8	XM_047449238.1 linkuse as main transcript	c.703C>G	p.Gln235Glu	missense_variant	6/8		XP_047305194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR8	ENST00000335754.8 linkuse as main transcript	c.1429C>G	p.Gln477Glu	missense_variant	11/13	2	NM_022899.5	ENSP00000336842	P1	Q9H981-1
ACTR8	ENST00000482349.5 linkuse as main transcript	c.1096C>G	p.Gln366Glu	missense_variant	11/13	2		ENSP00000419429		Q9H981-2
ACTR8	ENST00000486794.1 linkuse as main transcript	c.691C>G	p.Gln231Glu	missense_variant	6/8	2		ENSP00000417230
ACTR8	ENST00000495993.1 linkuse as main transcript	n.305C>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251426

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727242

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:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 05, 2022

The c.1429C>G (p.Q477E) alteration is located in exon 11 (coding exon 11) of the ACTR8 gene. This alteration results from a C to G substitution at nucleotide position 1429, causing the glutamine (Q) at amino acid position 477 to be replaced by a glutamic acid (E). 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

0.099

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

0.0024

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.054

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Benign

0.76

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.050

N;N

REVEL

Uncertain

0.43

Sift

Benign

0.57

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.0030

B;.

Vest4

0.36

MutPred

0.36

Gain of phosphorylation at S475 (P = 0.0907);.;

MVP

0.96

MPC

0.39

ClinPred

0.20

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.43

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