dbSNP rs371924812: ACTR8:p.Pro389Ser (chr3-53872521-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_022899.5(ACTR8):c.1165C>T(p.Pro389Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,596,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ACTR8
NM_022899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.63

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.763

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR8	NM_022899.5	MANE Select	c.1165C>T	p.Pro389Ser	missense	Exon 10 of 13	NP_075050.3
	ACTR8	NM_001410774.1		c.832C>T	p.Pro278Ser	missense	Exon 10 of 13	NP_001397703.1	Q9H981-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACTR8	ENST00000335754.8	TSL:2 MANE Select	c.1165C>T	p.Pro389Ser	missense	Exon 10 of 13	ENSP00000336842.3	Q9H981-1
ACTR8	ENST00000888053.1		c.1165C>T	p.Pro389Ser	missense	Exon 10 of 13	ENSP00000558112.1
ACTR8	ENST00000963856.1		c.1165C>T	p.Pro389Ser	missense	Exon 10 of 14	ENSP00000633915.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000427

AC:

AN:

234054

AF XY:

0.0000315

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000596

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000125

AC:

AN:

1444034

Hom.:

Cov.:

AF XY:

0.00000696

AC XY:

AN XY:

718446

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32170

American (AMR)

AF:

0.00

AC:

AN:

39390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25344

East Asian (EAS)

AF:

0.000385

AC:

AN:

38936

South Asian (SAS)

AF:

0.00

AC:

AN:

83226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106540

Other (OTH)

AF:

0.0000504

AC:

AN:

59572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000771

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.64

MetaRNN

Pathogenic

0.76

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

3.3

PhyloP100

9.6

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-7.0

REVEL

Pathogenic

0.86

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.94

MutPred

0.75

Gain of catalytic residue at P389 (P = 0.0267)

MVP

0.99

MPC

0.84

ClinPred

0.53

GERP RS

4.9

Varity_R

0.87

gMVP

0.77

Mutation Taster

=15/85

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over