Variant 3-53872433-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022899.5(ACTR8):c.1253A>T(p.Asp418Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,286 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: 6.9e-7 ( 0 hom. )

Consequence

ACTR8
NM_022899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR8	NM_022899.5 link	c.1253A>T	p.Asp418Val	missense_variant	Exon 10 of 13	ENST00000335754.8	NP_075050.3	Q9H981-1
ACTR8	NM_001410774.1 link	c.920A>T	p.Asp307Val	missense_variant	Exon 10 of 13		NP_001397703.1
ACTR8	XM_005265587.6 link	c.1253A>T	p.Asp418Val	missense_variant	Exon 10 of 14		XP_005265644.1	Q9H981-1
ACTR8	XM_047449238.1 link	c.527A>T	p.Asp176Val	missense_variant	Exon 5 of 8		XP_047305194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ACTR8	ENST00000335754.8 link	c.1253A>T	p.Asp418Val	missense_variant	Exon 10 of 13	2	NM_022899.5	ENSP00000336842.3	Q9H981-1
ACTR8	ENST00000482349.5 link	c.920A>T	p.Asp307Val	missense_variant	Exon 10 of 13	2		ENSP00000419429.1	Q9H981-2
ACTR8	ENST00000486794.1 link	c.512A>T	p.Asp171Val	missense_variant	Exon 5 of 8	2		ENSP00000417230.1	H0Y849
ACTR8	ENST00000495993.1 link	n.129A>T		non_coding_transcript_exon_variant	Exon 2 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459286

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725996

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:

9.00e-7

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

Mar 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1253A>T (p.D418V) alteration is located in exon 10 (coding exon 10) of the ACTR8 gene. This alteration results from a A to T substitution at nucleotide position 1253, causing the aspartic acid (D) at amino acid position 418 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

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.53

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;.

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.96

D;D

M_CAP

Uncertain

0.29

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.032

MutationAssessor

Pathogenic

3.2

M;.

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-8.8

D;D

REVEL

Pathogenic

0.78

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;.

Vest4

0.91

MutPred

0.52

Gain of loop (P = 0.0435);.;

MVP

0.99

MPC

1.1

ClinPred

1.0

GERP RS

6.2

Varity_R

0.85

gMVP

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over