NM_005717.4:c.351G>A

Variant names:

• chr1-183630503-C-T
• rs2231240
• NM_005717.4:c.351G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.308
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 113 with autoimmunity and autoinflammation

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005717.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC5	NM_005717.4	MANE Select	c.351G>A	p.Pro117Pro	synonymous	Exon 3 of 4	NP_005708.1	O15511-1
	ARPC5	NM_001270439.2		c.360G>A	p.Pro120Pro	synonymous	Exon 3 of 4	NP_001257368.1	O15511-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC5	ENST00000359856.11	TSL:1 MANE Select	c.351G>A	p.Pro117Pro	synonymous	Exon 3 of 4	ENSP00000352918.6	O15511-1
	ARPC5	ENST00000294742.6	TSL:1	c.360G>A	p.Pro120Pro	synonymous	Exon 3 of 4	ENSP00000294742.6	O15511-2
	ARPC5	ENST00000367534.5	TSL:3	c.351G>A	p.Pro117Pro	synonymous	Exon 3 of 4	ENSP00000356504.1	B1ALC0

Frequencies

GnomAD3 genomes AF: 0.0790 AC: 12017 AN: 152102 Hom.: 919 Cov.: 32

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

GnomAD2 exomes AF: 0.0460 AC: 11556 AN: 251012 AF XY: 0.0450

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 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.: 30 AF XY: 0.0362 AC XY: 26308 AN XY: 726886

African (AFR) AF: 0.214 AC: 7142 AN: 33440

American (AMR) AF: 0.0195 AC: 870 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.0136 AC: 354 AN: 26112

East Asian (EAS) AF: 0.0450 AC: 1786 AN: 39682

South Asian (SAS) AF: 0.0661 AC: 5698 AN: 86166

European-Finnish (FIN) AF: 0.0264 AC: 1407 AN: 53306

Middle Eastern (MID) AF: 0.0502 AC: 289 AN: 5762

European-Non Finnish (NFE) AF: 0.0289 AC: 32142 AN: 1111558

Other (OTH) AF: 0.0441 AC: 2659 AN: 60358

GnomAD4 genome AF: 0.0791 AC: 12033 AN: 152220 Hom.: 925 Cov.: 32 AF XY: 0.0771 AC XY: 5735 AN XY: 74426

African (AFR) AF: 0.200 AC: 8294 AN: 41516

American (AMR) AF: 0.0381 AC: 582 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3470

East Asian (EAS) AF: 0.0809 AC: 419 AN: 5182

South Asian (SAS) AF: 0.0634 AC: 306 AN: 4828

European-Finnish (FIN) AF: 0.0262 AC: 277 AN: 10588

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1953 AN: 68034

Other (OTH) AF: 0.0636 AC: 134 AN: 2106

Alfa AF: 0.0522 Hom.: 290

Bravo AF: 0.0858

Asia WGS AF: 0.0740 AC: 256 AN: 3478

EpiCase AF: 0.0303

EpiControl AF: 0.0285

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	12
DANN	Benign	0.54
PhyloP100		-0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2231240; hg19: chr1-183599638; COSMIC: COSV54171109;