Variant 7-99385753-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_005720.4(ARPC1B):c.39C>G(p.Cys13Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,610,896 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ARPC1B
NM_005720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

ARPC1B (HGNC:704): (actin related protein 2/3 complex subunit 1B) This gene encodes one of seven subunits of the human Arp2/3 protein complex. This subunit is a member of the SOP2 family of proteins and is most similar to the protein encoded by gene ARPC1A. The similarity between these two proteins suggests that they both may function as p41 subunit of the human Arp2/3 complex that has been implicated in the control of actin polymerization in cells. It is possible that the p41 subunit is involved in assembling and maintaining the structure of the Arp2/3 complex. Multiple versions of the p41 subunit may adapt the functions of the complex to different cell types or developmental stages. This protein also has a role in centrosomal homeostasis by being an activator and substrate of the Aurora A kinase. [provided by RefSeq, Mar 2011]

ARPC1B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.907

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC1B	NM_005720.4 linkuse as main transcript	c.39C>G	p.Cys13Trp	missense_variant	2/10	ENST00000646101.2	NP_005711.1
ARPC1B	XM_024446628.2 linkuse as main transcript	c.39C>G	p.Cys13Trp	missense_variant	2/10		XP_024302396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC1B	ENST00000646101.2 linkuse as main transcript	c.39C>G	p.Cys13Trp	missense_variant	2/10		NM_005720.4	ENSP00000496599	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458684

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.39C>G (p.C13W) alteration is located in exon 2 (coding exon 1) of the ARPC1B gene. This alteration results from a C to G substitution at nucleotide position 39, causing the cysteine (C) at amino acid position 13 to be replaced by a tryptophan (W). 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

0.99

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

.;T;.;T;T;T;.;T;.;T;T;T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.76

LIST_S2

Uncertain

0.97

D;D;D;.;.;.;D;D;D;.;.;.;.;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.91

D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.1

.;.;.;M;M;M;.;.;.;M;M;M;M;M

MutationTaster

Benign

0.99

N;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-8.7

.;D;D;.;D;D;D;D;D;D;D;D;D;.

REVEL

Uncertain

0.64

Sift

Uncertain

0.013

.;D;D;.;D;D;D;.;D;D;D;D;D;.

Sift4G

Uncertain

0.013

.;D;D;.;D;D;D;D;D;D;D;D;D;.

Polyphen

1.0

.;.;.;D;D;D;.;.;.;D;D;D;D;D

Vest4

0.85, 0.84

MutPred

0.71

.;Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);Loss of ubiquitination at K18 (P = 0.0863);

MVP

0.79

MPC

1.4

ClinPred

1.0

GERP RS

2.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.93

gMVP

0.75

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