7-99344322-A-G

Position:

• chr7-99344322-A-G

Variant summary

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

The NM_006409.4(ARPC1A):​c.199A>G​(p.Ile67Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARPC1A NM_006409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.31

Genes affected

ARPC1A (HGNC:703): (actin related protein 2/3 complex subunit 1A) 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 ARPC1B. 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

ENSG00000284292 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
ARPC1A	NM_006409.4	c.199A>G	p.Ile67Val	missense_variant	4/10	ENST00000262942.10	NP_006400.2
ARPC1A	NM_001190996.2	c.157A>G	p.Ile53Val	missense_variant	4/10		NP_001177925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC1A	ENST00000262942.10	c.199A>G	p.Ile67Val	missense_variant	4/10	1	NM_006409.4	ENSP00000262942.5
ENSG00000284292	ENST00000638617.1	c.199A>G	p.Ile67Val	missense_variant	4/17	5		ENSP00000491073.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.199A>G (p.I67V) alteration is located in exon 4 (coding exon 3) of the ARPC1A gene. This alteration results from a A to G substitution at nucleotide position 199, causing the isoleucine (I) at amino acid position 67 to be replaced by a valine (V). 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	Uncertain	0.50
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.040	.;T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.85	D;D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.93	.;N
REVEL	Benign	0.29
Sift	Uncertain	0.0020	.;D
Sift4G	Uncertain	0.0040	.;D
Polyphen		0.41	.;B
Vest4		0.71
MutPred		0.79		Gain of ubiquitination at K63 (P = 0.0882);Gain of ubiquitination at K63 (P = 0.0882);
MVP		0.70
MPC		1.1
ClinPred		0.78	D
GERP RS		5.4
Varity_R		0.28
gMVP		0.26

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: chr7-98941945;