Variant 3-53868757-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_022899.5(ACTR8):c.1837G>A(p.Val613Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,884 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: 0.0000021 ( 0 hom. )

Consequence

ACTR8
NM_022899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33965132).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR8	NM_022899.5 link	c.1837G>A	p.Val613Ile	missense_variant	Exon 13 of 13	ENST00000335754.8	NP_075050.3	Q9H981-1
ACTR8	NM_001410774.1 link	c.1504G>A	p.Val502Ile	missense_variant	Exon 13 of 13		NP_001397703.1
ACTR8	XM_005265587.6 link	c.1837G>A	p.Val613Ile	missense_variant	Exon 13 of 14		XP_005265644.1	Q9H981-1
ACTR8	XM_047449238.1 link	c.1111G>A	p.Val371Ile	missense_variant	Exon 8 of 8		XP_047305194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACTR8	ENST00000335754.8 link	c.1837G>A	p.Val613Ile	missense_variant	Exon 13 of 13	2	NM_022899.5	ENSP00000336842.3	Q9H981-1
ACTR8	ENST00000482349.5 link	c.1504G>A	p.Val502Ile	missense_variant	Exon 13 of 13	2		ENSP00000419429.1	Q9H981-2
ACTR8	ENST00000486794.1 link	c.1096G>A	p.Val366Ile	missense_variant	Exon 8 of 8	2		ENSP00000417230.1	H0Y849
ACTR8	ENST00000488802.1 link	n.422G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251444

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

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:

0.00000205

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

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:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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.1837G>A (p.V613I) alteration is located in exon 13 (coding exon 13) of the ACTR8 gene. This alteration results from a G to A substitution at nucleotide position 1837, causing the valine (V) at amino acid position 613 to be replaced by an isoleucine (I). 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

0.085

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Benign

0.056

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.080

MetaRNN

Benign

0.34

T;T

MetaSVM

Uncertain

0.47

MutationAssessor

Benign

1.8

L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.22

N;N

REVEL

Uncertain

0.39

Sift

Benign

0.097

T;D

Sift4G

Benign

0.29

T;T

Polyphen

0.34

B;.

Vest4

0.38

MutPred

0.64

Loss of helix (P = 0.1299);.;

MVP

0.86

MPC

0.55

ClinPred

0.52

GERP RS

5.9

Varity_R

0.10

gMVP

0.34

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