Variant 7-150284763-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001164458.2(ACTR3C):c.554C>T(p.Pro185Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000509 in 1,612,270 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P185S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

ACTR3C
NM_001164458.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACTR3C	NM_001164458.2 linkuse as main transcript	c.554C>T	p.Pro185Leu	missense_variant	6/8	ENST00000683684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACTR3C	ENST00000683684.1 linkuse as main transcript	c.554C>T	p.Pro185Leu	missense_variant	6/8		NM_001164458.2	P1	Q9C0K3-1
ACTR3C	ENST00000252071.8 linkuse as main transcript	c.554C>T	p.Pro185Leu	missense_variant	6/8	1		P1	Q9C0K3-1
ACTR3C	ENST00000478393.5 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	5/6	1
ACTR3C	ENST00000539352.5 linkuse as main transcript	c.554C>T	p.Pro185Leu	missense_variant	5/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000641

AC:

AN:

249598

Hom.:

AF XY:

0.0000593

AC XY:

AN XY:

134938

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.000219

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000531

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1460288

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726424

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000260

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 22, 2023

The c.554C>T (p.P185L) alteration is located in exon 6 (coding exon 5) of the ACTR3C gene. This alteration results from a C to T substitution at nucleotide position 554, causing the proline (P) at amino acid position 185 to be replaced by a leucine (L). 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

Benign

0.32

BayesDel_addAF

Benign

0.0012

BayesDel_noAF

Uncertain

0.060

Cadd

Pathogenic

Dann

Uncertain

0.99

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Uncertain

0.68

MutationTaster

Benign

1.0

D;D

PROVEAN

Uncertain

-2.9

D;D;D

REVEL

Pathogenic

0.75

Sift

Benign

0.034

D;D;D

Sift4G

Uncertain

0.030

D;T;T

Polyphen

1.0

.;D;.

Vest4

0.83, 0.77

MutPred

0.55

.;Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);

MVP

0.92

MPC

0.42

ClinPred

0.30

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.54

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over