Genetic Variant ARPC5:p.Pro117Pro (chr1-183630503-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_005717.4(ARPC5):c.351G>A(p.Pro117Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,613,282 control chromosomes in the GnomAD database, including 2,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 925 hom., cov: 32)

Exomes 𝑓: 0.036 ( 1679 hom. )

Consequence

ARPC5
NM_005717.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.308

Variant links:

Genes affected

ARPC5 (HGNC:708): (actin related protein 2/3 complex subunit 5) This gene encodes one of seven subunits of the human Arp2/3 protein complex. The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells and has been conserved through evolution. The exact role of the protein encoded by this gene, the p16 subunit, has yet to be determined. Alternatively spliced transcript variants encoding different isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

ARPC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 1-183630503-C-T is Benign according to our data. Variant chr1-183630503-C-T is described in ClinVar as [Benign]. Clinvar id is 1247938.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.308 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC5	NM_005717.4 link	c.351G>A	p.Pro117Pro	synonymous_variant	Exon 3 of 4	ENST00000359856.11	NP_005708.1	O15511-1
ARPC5	NM_001270439.2 link	c.360G>A	p.Pro120Pro	synonymous_variant	Exon 3 of 4		NP_001257368.1	O15511-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC5	ENST00000359856.11 link	c.351G>A	p.Pro117Pro	synonymous_variant	Exon 3 of 4	1	NM_005717.4	ENSP00000352918.6		O15511-1

Frequencies

GnomAD3 genomes

AF:

0.0790

AC:

12017

AN:

152102

Hom.:

919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.200

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.0381

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.0803

Gnomad SAS

AF:

0.0631

Gnomad FIN

AF:

0.0262

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0287

Gnomad OTH

AF:

0.0648

GnomAD3 exomes

AF:

0.0460

AC:

11556

AN:

251012

Hom.:

540

AF XY:

0.0450

AC XY:

6105

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.203

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0124

Gnomad EAS exome

AF:

0.0831

Gnomad SAS exome

AF:

0.0658

Gnomad FIN exome

AF:

0.0271

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0358

AC:

52347

AN:

1461062

Hom.:

1679

Cov.:

AF XY:

0.0362

AC XY:

26308

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.0195

Gnomad4 ASJ exome

AF:

0.0136

Gnomad4 EAS exome

AF:

0.0450

Gnomad4 SAS exome

AF:

0.0661

Gnomad4 FIN exome

AF:

0.0264

Gnomad4 NFE exome

AF:

0.0289

Gnomad4 OTH exome

AF:

0.0441

GnomAD4 genome

AF:

0.0791

AC:

12033

AN:

152220

Hom.:

925

Cov.:

AF XY:

0.0771

AC XY:

5735

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.0381

Gnomad4 ASJ

AF:

0.0130

Gnomad4 EAS

AF:

0.0809

Gnomad4 SAS

AF:

0.0634

Gnomad4 FIN

AF:

0.0262

Gnomad4 NFE

AF:

0.0287

Gnomad4 OTH

AF:

0.0636

Alfa

AF:

0.0521

Hom.:

229

Bravo

AF:

0.0858

Asia WGS

AF:

0.0740

AC:

256

AN:

3478

EpiCase

AF:

0.0303

EpiControl

AF:

0.0285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.54

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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