1-183635637-G-T

Position:

• chr1-183635637-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_005717.4(ARPC5):​c.23C>A​(p.Ser8*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARPC5 NM_005717.4 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.14

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.95 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-183635637-G-T is Pathogenic according to our data. Variant chr1-183635637-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 2663870.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC5	NM_005717.4	c.23C>A	p.Ser8*	stop_gained	1/4	ENST00000359856.11	NP_005708.1
ARPC5	NM_001270439.2	c.23C>A	p.Ser8*	stop_gained	1/4		NP_001257368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC5	ENST00000359856.11	c.23C>A	p.Ser8*	stop_gained	1/4	1	NM_005717.4	ENSP00000352918.6
ARPC5	ENST00000294742.6	c.23C>A	p.Ser8*	stop_gained	1/4	1		ENSP00000294742.6
ARPC5	ENST00000367534.5	c.23C>A	p.Ser8*	stop_gained	1/4	3		ENSP00000356504.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 113 with autoimmunity and autoinflammation Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Nov 17, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.63
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Pathogenic	0.74
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.99	D
Vest4		0.22
GERP RS		5.5
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-183604772;