Genetic Variant ACTR3C:p.Asp108Asn (chr7-150286516-C-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001164458.2(ACTR3C):c.322G>A(p.Asp108Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000267 in 1,611,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D108H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.41

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3765816).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164458.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACTR3C	NM_001164458.2	MANE Select	c.322G>A	p.Asp108Asn	missense	Exon 5 of 8	NP_001157930.1	Q9C0K3-1
ACTR3C	NM_001164459.2		c.322G>A	p.Asp108Asn	missense	Exon 5 of 8	NP_001157931.1	Q9C0K3-1
ACTR3C	NM_001351028.2		c.-220G>A		5_prime_UTR	Exon 5 of 10	NP_001337957.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ACTR3C	ENST00000683684.1	MANE Select	c.322G>A	p.Asp108Asn	missense	Exon 5 of 8	ENSP00000507618.1	Q9C0K3-1
ACTR3C	ENST00000252071.8	TSL:1	c.322G>A	p.Asp108Asn	missense	Exon 5 of 8	ENSP00000252071.4	Q9C0K3-1
ACTR3C	ENST00000478393.5	TSL:1	c.316G>A	p.Asp106Asn	missense	Exon 4 of 6	ENSP00000417426.1	H7C4J1

Frequencies

GnomAD3 genomes

AF:

0.0000864

AC:

AN:

150458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000744

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000659

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000598

AC:

AN:

250732

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1460778

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

726588

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33274

American (AMR)

AF:

0.000246

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1111820

Other (OTH)

AF:

0.00

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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:

0.0000864

AC:

AN:

150458

Hom.:

Cov.:

AF XY:

0.0000818

AC XY:

AN XY:

73366

show subpopulations

African (AFR)

AF:

0.0000744

AC:

AN:

40312

American (AMR)

AF:

0.000659

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4704

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67938

Other (OTH)

AF:

0.00

AC:

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.000136

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

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

Benign

0.22

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0019

MetaRNN

Benign

0.38

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

PhyloP100

4.4

PROVEAN

Pathogenic

-4.5

REVEL

Benign

0.17

Sift

Benign

0.097

Sift4G

Uncertain

0.048

Polyphen

0.99

Vest4

0.57

MutPred

0.67

Loss of catalytic residue at D108 (P = 0.0362)

MVP

0.26

MPC

0.40

ClinPred

0.80

GERP RS

2.5

Varity_R

0.41

gMVP

0.61

Mutation Taster

=78/22

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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