NM_022899.5:c.1379C>G

Variant names:

• chr3-53871420-G-C
• NM_022899.5:c.1379C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_022899.5(ACTR8):​c.1379C>G​(p.Ser460Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,858 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: 6.8e-7 (0 hom.)
• Consequence: ACTR8 NM_022899.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.88

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32502604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR8	NM_022899.5	c.1379C>G	p.Ser460Cys	missense_variant	Exon 11 of 13	ENST00000335754.8	NP_075050.3
ACTR8	NM_001410774.1	c.1046C>G	p.Ser349Cys	missense_variant	Exon 11 of 13		NP_001397703.1
ACTR8	XM_005265587.6	c.1379C>G	p.Ser460Cys	missense_variant	Exon 11 of 14		XP_005265644.1
ACTR8	XM_047449238.1	c.653C>G	p.Ser218Cys	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.1379C>G	p.Ser460Cys	missense_variant	Exon 11 of 13	2	NM_022899.5	ENSP00000336842.3
ACTR8	ENST00000482349.5	c.1046C>G	p.Ser349Cys	missense_variant	Exon 11 of 13	2		ENSP00000419429.1
ACTR8	ENST00000486794.1	c.638C>G	p.Ser213Cys	missense_variant	Exon 6 of 8	2		ENSP00000417230.1
ACTR8	ENST00000495993.1	n.255C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461858 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.96
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.067	T;T
Sift4G	Benign	0.065	T;T
Polyphen		0.0020	B;.
Vest4		0.43
MVP		0.97
MPC		0.25
ClinPred		0.71	D
GERP RS		5.9
Varity_R		0.080
gMVP		0.42

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.

Other links and lift over

hg19: chr3-53905447;