Genetic Variant ACTR3C:p.Arg32His (chr7-150293370-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001164458.2(ACTR3C):c.95G>A(p.Arg32His) variant causes a missense change. The variant allele was found at a frequency of 0.000028 in 1,608,304 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.42

Publications

1 publications found

Variant links:

Genes affected

ACTR3C (HGNC:37282): (actin related protein 3C) Predicted to enable ATP binding activity. Predicted to contribute to actin filament binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACTR3C links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2 link	c.95G>A	p.Arg32His	missense_variant	Exon 3 of 8	ENST00000683684.1	NP_001157930.1	Q9C0K3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTR3C	ENST00000683684.1 link	c.95G>A	p.Arg32His	missense_variant	Exon 3 of 8		NM_001164458.2	ENSP00000507618.1		Q9C0K3-1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000534

AC:

AN:

243398

AF XY:

0.0000534

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000820

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1456146

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

723574

show subpopulations

African (AFR)

AF:

0.0000897

AC:

AN:

33432

American (AMR)

AF:

0.0000226

AC:

AN:

44208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25934

East Asian (EAS)

AF:

0.00

AC:

AN:

39654

South Asian (SAS)

AF:

0.00

AC:

AN:

84900

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53102

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000307

AC:

AN:

1108940

Other (OTH)

AF:

0.0000166

AC:

AN:

60214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41492

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000906

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.55

D;.;.;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.82

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Uncertain

0.61

MutationAssessor

Pathogenic

3.5

H;.;.;.

PhyloP100

4.4

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Uncertain

0.37

Sift

Benign

0.063

T;T;T;D

Sift4G

Uncertain

0.046

D;T;.;D

Polyphen

0.98

D;.;.;.

Vest4

0.45

MVP

0.91

MPC

0.65

ClinPred

0.58

GERP RS

0.85

Varity_R

0.068

gMVP

0.57

Mutation Taster

=85/15

polymorphism

(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

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chr7-150293370-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over