7-99385772-C-A

Variant names:

Variant summary

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

The NM_005720.4(ARPC1B):c.58C>A(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,609,408 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. R20C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ARPC1B
NM_005720.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.885

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:

ENSG00000284292 (HGNC:):

ENSG00000284292 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 rank	MANE	Protein	UniProt
ARPC1B	NM_005720.4 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 2 of 10	ENST00000646101.2	NP_005711.1	O15143A4D275
ARPC1B	XM_024446628.2 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 2 of 10		XP_024302396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC1B	ENST00000646101.2 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 2 of 10		NM_005720.4	ENSP00000496599.1		O15143
ENSG00000284292	ENST00000638617.1 link	c.1054C>A	p.Arg352Ser	missense_variant	Exon 9 of 17	5		ENSP00000491073.1		A0A1W2PNV4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

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

GnomAD3 exomes

AF:

0.00000417

AC:

AN:

240064

Hom.:

AF XY:

0.00000769

AC XY:

AN XY:

130004

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000916

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1457210

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

724502

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:

0.0000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

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

Jan 18, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.58C>A (p.R20S) alteration is located in exon 2 (coding exon 1) of the ARPC1B gene. This alteration results from a C to A substitution at nucleotide position 58, causing the arginine (R) at amino acid position 20 to be replaced by a serine (S). 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

0.71

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

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

Eigen

Benign

0.17

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.97

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

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.68

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

MetaSVM

Benign

-0.59

MutationAssessor

Uncertain

2.9

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

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.2

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

REVEL

Uncertain

0.34

Sift

Uncertain

0.0050

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

Sift4G

Uncertain

0.012

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

Polyphen

0.73

.;.;.;P;P;P;.;.;.;P;P;P;P;P

Vest4

0.77, 0.76

MutPred

0.55

.;Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);Gain of glycosylation at R20 (P = 0.0192);

MVP

0.74

MPC

0.50

ClinPred

0.92

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.66

gMVP

0.57

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