3-53875704-C-A

Position:

• chr3-53875704-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022899.5(ACTR8):​c.911+244G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,134 control chromosomes in the GnomAD database, including 25,998 homozygotes. 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: 𝑓 0.57 (25998 hom., cov: 33)
• Consequence: ACTR8 NM_022899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACTR8	NM_022899.5	c.911+244G>T		intron_variant		ENST00000335754.8	NP_075050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACTR8	ENST00000335754.8	c.911+244G>T		intron_variant		2	NM_022899.5	ENSP00000336842	P1
ACTR8	ENST00000482349.5	c.578+244G>T		intron_variant		2		ENSP00000419429
ACTR8	ENST00000486794.1	c.307+244G>T		intron_variant		2		ENSP00000417230

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85880 AN: 152016 Hom.: 25939 Cov.: 33

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.534

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.565 AC: 85996 AN: 152134 Hom.: 25998 Cov.: 33 AF XY: 0.571 AC XY: 42438 AN XY: 74380

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.536

Alfa AF: 0.473 Hom.: 35522

Bravo AF: 0.586

Asia WGS AF: 0.809 AC: 2813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.080
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs893367; hg19: chr3-53909731;