Variant 3-53870067-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_022899.5(ACTR8):c.1646A>G(p.Glu549Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 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: 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: 7.63

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:

Genome browser will be placed here

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, 0.831

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR8	NM_022899.5 link	c.1646A>G	p.Glu549Gly	missense_variant	Exon 12 of 13	ENST00000335754.8	NP_075050.3	Q9H981-1
ACTR8	NM_001410774.1 link	c.1313A>G	p.Glu438Gly	missense_variant	Exon 12 of 13		NP_001397703.1
ACTR8	XM_005265587.6 link	c.1646A>G	p.Glu549Gly	missense_variant	Exon 12 of 14		XP_005265644.1	Q9H981-1
ACTR8	XM_047449238.1 link	c.920A>G	p.Glu307Gly	missense_variant	Exon 7 of 8		XP_047305194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACTR8	ENST00000335754.8 link	c.1646A>G	p.Glu549Gly	missense_variant	Exon 12 of 13	2	NM_022899.5	ENSP00000336842.3	Q9H981-1
ACTR8	ENST00000482349.5 link	c.1313A>G	p.Glu438Gly	missense_variant	Exon 12 of 13	2		ENSP00000419429.1	Q9H981-2
ACTR8	ENST00000486794.1 link	c.905A>G	p.Glu302Gly	missense_variant	Exon 7 of 8	2		ENSP00000417230.1	H0Y849
ACTR8	ENST00000488802.1 link	n.231A>G		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251478

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

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:

0.00000137

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

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

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1646A>G (p.E549G) alteration is located in exon 12 (coding exon 12) of the ACTR8 gene. This alteration results from a A to G substitution at nucleotide position 1646, causing the glutamic acid (E) at amino acid position 549 to be replaced by a glycine (G). 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

0.21

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.058

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.8

L;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.2

N;N

REVEL

Pathogenic

0.80

Sift

Benign

0.29

T;T

Sift4G

Benign

0.34

T;T

Polyphen

0.020

B;.

Vest4

0.90

MutPred

0.64

Gain of MoRF binding (P = 0.0534);.;

MVP

0.99

MPC

0.30

ClinPred

0.64

GERP RS

5.2

Varity_R

0.33

gMVP

0.61

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