3-53871351-G-A

Variant names:

• chr3-53871351-G-A
• NM_022899.5:c.1448C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022899.5(ACTR8):​c.1448C>T​(p.Ala483Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACTR8 NM_022899.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

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]

ACMG classification

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=0.17673579).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR8	NM_022899.5	c.1448C>T	p.Ala483Val	missense_variant	Exon 11 of 13	ENST00000335754.8	NP_075050.3
ACTR8	NM_001410774.1	c.1115C>T	p.Ala372Val	missense_variant	Exon 11 of 13		NP_001397703.1
ACTR8	XM_005265587.6	c.1448C>T	p.Ala483Val	missense_variant	Exon 11 of 14		XP_005265644.1
ACTR8	XM_047449238.1	c.722C>T	p.Ala241Val	missense_variant	Exon 6 of 8		XP_047305194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR8	ENST00000335754.8	c.1448C>T	p.Ala483Val	missense_variant	Exon 11 of 13	2	NM_022899.5	ENSP00000336842.3
ACTR8	ENST00000482349.5	c.1115C>T	p.Ala372Val	missense_variant	Exon 11 of 13	2		ENSP00000419429.1
ACTR8	ENST00000486794.1	c.707C>T	p.Ala236Val	missense_variant	Exon 6 of 8	2		ENSP00000417230.1
ACTR8	ENST00000495993.1	n.324C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1448C>T (p.A483V) alteration is located in exon 11 (coding exon 11) of the ACTR8 gene. This alteration results from a C to T substitution at nucleotide position 1448, causing the alanine (A) at amino acid position 483 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	Benign	0.079
BayesDel_addAF	Uncertain	0.094	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Benign	0.77
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.1	N;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.0	N;N
REVEL	Uncertain	0.42
Sift	Benign	0.34	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.17	B;.
Vest4		0.12
MutPred		0.36		Gain of sheet (P = 0.0827);.;
MVP		0.96
MPC		0.25
ClinPred		0.39	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.020
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr3-53905378;