1-183635564-G-A

Variant names:

• chr1-183635564-G-A
• rs376202902
• NM_005717.4:c.96C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005717.4(ARPC5):​c.96C>T​(p.Asp32Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ARPC5 NM_005717.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 1 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-0.19 with no splicing effect.

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.96C>T	p.Asp32Asp	synonymous	Exon 1 of 4	NP_005708.1	O15511-1
	ARPC5	NM_001270439.2		c.96C>T	p.Asp32Asp	synonymous	Exon 1 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.96C>T	p.Asp32Asp	synonymous	Exon 1 of 4	ENSP00000352918.6	O15511-1
	ARPC5	ENST00000294742.6	TSL:1	c.96C>T	p.Asp32Asp	synonymous	Exon 1 of 4	ENSP00000294742.6	O15511-2
	ARPC5	ENST00000367534.5	TSL:3	c.96C>T	p.Asp32Asp	synonymous	Exon 1 of 4	ENSP00000356504.1	B1ALC0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1460916 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726750

African (AFR) AF: 0.00 AC: 0 AN: 33454

American (AMR) AF: 0.00 AC: 0 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53040

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111752

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		-0.19
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs376202902; hg19: chr1-183604699;