dbSNP rs749903138: ACTR3C:p.Thr72Ala (chr7-150289533-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001164458.2(ACTR3C):c.214A>G(p.Thr72Ala) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000015 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29

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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTR3C	NM_001164458.2 link	c.214A>G	p.Thr72Ala	missense_variant	Exon 4 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.214A>G	p.Thr72Ala	missense_variant	Exon 4 of 8		NM_001164458.2	ENSP00000507618.1		Q9C0K3-1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151634

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:

0.00

Gnomad SAS

AF:

0.000631

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000862

AC:

AN:

231966

AF XY:

0.0000160

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000151

AC:

AN:

1453476

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721546

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33174

American (AMR)

AF:

0.00

AC:

AN:

44464

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25888

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.000236

AC:

AN:

84588

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107014

Other (OTH)

AF:

0.0000167

AC:

AN:

60060

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000001), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.370

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000198

AC:

AN:

151634

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41128

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000631

AC:

AN:

4758

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.214A>G (p.T72A) alteration is located in exon 4 (coding exon 3) of the ACTR3C gene. This alteration results from a A to G substitution at nucleotide position 214, causing the threonine (T) at amino acid position 72 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.64

.;D;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

D;D;D;D

M_CAP

Benign

0.0035

MetaRNN

Uncertain

0.64

D;D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Pathogenic

4.6

.;H;.;.

PhyloP100

7.3

PROVEAN

Uncertain

-4.3

D;D;D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;.

Polyphen

0.86

.;P;.;.

Vest4

0.90, 0.89

MutPred

0.69

.;Gain of catalytic residue at T72 (P = 0.1148);Gain of catalytic residue at T72 (P = 0.1148);.;

MVP

0.57

MPC

2.4

ClinPred

0.94

GERP RS

2.0

Varity_R

0.63

gMVP

0.73

Mutation Taster

=62/38

polymorphism

(source)

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

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

rs749903138

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over