Variant 3-53873078-G-C 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.1115C>G(p.Ser372Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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: 7.56

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=0.3827073).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR8	NM_022899.5 linkuse as main transcript	c.1115C>G	p.Ser372Cys	missense_variant	9/13	ENST00000335754.8	NP_075050.3	Q9H981-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ACTR8	ENST00000335754.8 linkuse as main transcript	c.1115C>G	p.Ser372Cys	missense_variant	9/13	2	NM_022899.5	ENSP00000336842.3	Q9H981-1
ACTR8	ENST00000482349.5 linkuse as main transcript	c.782C>G	p.Ser261Cys	missense_variant	9/13	2		ENSP00000419429.1	Q9H981-2
ACTR8	ENST00000486794.1 linkuse as main transcript	c.374C>G	p.Ser125Cys	missense_variant	4/8	2		ENSP00000417230.1	H0Y849
ACTR8	ENST00000495993.1 linkuse as main transcript	n.-10C>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459738

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725886

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.1115C>G (p.S372C) alteration is located in exon 9 (coding exon 9) of the ACTR8 gene. This alteration results from a C to G substitution at nucleotide position 1115, causing the serine (S) at amino acid position 372 to be replaced by a cysteine (C). 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

0.065

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Benign

0.94

DEOGEN2

Benign

0.037

T;.

Eigen

Benign

0.056

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.75

T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.38

T;T

MetaSVM

Pathogenic

0.87

MutationAssessor

Benign

1.3

L;.

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-2.3

N;N

REVEL

Uncertain

0.52

Sift

Benign

0.066

T;T

Sift4G

Benign

0.077

T;T

Polyphen

0.0050

B;.

Vest4

0.33

MutPred

0.61

Loss of disorder (P = 0.0161);.;

MVP

0.96

MPC

0.25

ClinPred

0.79

GERP RS

5.3

Varity_R

0.47

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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