7-99338250-C-T

Variant names:

• chr7-99338250-C-T
• rs1793290378
• NM_006409.4:c.134C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006409.4(ARPC1A):​c.134C>T​(p.Ala45Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ARPC1A NM_006409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.64

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10711661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARPC1A	NM_006409.4	c.134C>T	p.Ala45Val	missense_variant	Exon 3 of 10	ENST00000262942.10	NP_006400.2
ARPC1A	NM_001190996.2	c.92C>T	p.Ala31Val	missense_variant	Exon 3 of 10		NP_001177925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARPC1A	ENST00000262942.10	c.134C>T	p.Ala45Val	missense_variant	Exon 3 of 10	1	NM_006409.4	ENSP00000262942.5
ENSG00000284292	ENST00000638617.1	c.134C>T	p.Ala45Val	missense_variant	Exon 3 of 17	5		ENSP00000491073.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460682 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726578

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 16, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.134C>T (p.A45V) alteration is located in exon 3 (coding exon 2) of the ARPC1A gene. This alteration results from a C to T substitution at nucleotide position 134, causing the alanine (A) at amino acid position 45 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	Benign	0.075
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	21
DANN	Benign	0.95
DEOGEN2	Benign	0.011	.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.048
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.43	.;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.18	.;N
REVEL	Benign	0.074
Sift	Benign	0.54	.;T
Sift4G	Benign	0.37	.;T
Polyphen		0.0	.;B
Vest4		0.17
MutPred		0.27		Gain of methylation at K44 (P = 0.0377);Gain of methylation at K44 (P = 0.0377);
MVP		0.33
MPC		0.82
ClinPred		0.50	T
GERP RS		5.8
Varity_R		0.049
gMVP		0.15

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

Other links and lift over

dbSNP: rs1793290378; hg19: chr7-98935873;