3-53868727-C-T

Position:

• chr3-53868727-C-T

Variant summary

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

The NM_022899.5(ACTR8):​c.1867G>A​(p.Val623Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.48

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR8	NM_022899.5	c.1867G>A	p.Val623Met	missense_variant	13/13	ENST00000335754.8	NP_075050.3
ACTR8	NM_001410774.1	c.1534G>A	p.Val512Met	missense_variant	13/13		NP_001397703.1
ACTR8	XM_005265587.6	c.1867G>A	p.Val623Met	missense_variant	13/14		XP_005265644.1
ACTR8	XM_047449238.1	c.1141G>A	p.Val381Met	missense_variant	8/8		XP_047305194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR8	ENST00000335754.8	c.1867G>A	p.Val623Met	missense_variant	13/13	2	NM_022899.5	ENSP00000336842	P1
ACTR8	ENST00000482349.5	c.1534G>A	p.Val512Met	missense_variant	13/13	2		ENSP00000419429
ACTR8	ENST00000486794.1	c.1129G>A	p.Val377Met	missense_variant	8/8	2		ENSP00000417230
ACTR8	ENST00000488802.1	n.452G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.1867G>A (p.V623M) 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 1867, causing the valine (V) at amino acid position 623 to be replaced by a methionine (M). 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	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T;.
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Uncertain	0.78	D
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.050	N;N
REVEL	Uncertain	0.54
Sift	Benign	0.45	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.23	B;.
Vest4		0.66
MutPred		0.33		Gain of disorder (P = 0.0442);.;
MVP		0.96
MPC		0.49
ClinPred		0.80	D
GERP RS		5.9
Varity_R		0.12
gMVP		0.38

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.

Other links and lift over

hg19: chr3-53902754;