chr7-99359584-C-T

Variant names:

• chr7-99359584-C-T
• rs187071817
• NM_006409.4:c.829C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_006409.4(ARPC1A):​c.829C>T​(p.Arg277Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R277G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: ARPC1A NM_006409.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.070171535).
• BS2: High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006409.4. 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
	ARPC1A	NM_006409.4	MANE Select	c.829C>T	p.Arg277Cys	missense	Exon 8 of 10	NP_006400.2
	ARPC1A	NM_001190996.2		c.787C>T	p.Arg263Cys	missense	Exon 8 of 10	NP_001177925.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARPC1A	ENST00000262942.10	TSL:1 MANE Select	c.829C>T	p.Arg277Cys	missense	Exon 8 of 10	ENSP00000262942.5	Q92747-1
	ENSG00000284292	ENST00000638617.1	TSL:5	c.829C>T	p.Arg277Cys	missense	Exon 8 of 17	ENSP00000491073.1	A0A1W2PNV4
	ARPC1A	ENST00000899462.1		c.895C>T	p.Arg299Cys	missense	Exon 8 of 10	ENSP00000569521.1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152090 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000795 AC: 20 AN: 251444 AF XY: 0.0000662

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000383 AC: 56 AN: 1461888 Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23 AN XY: 727246

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000554 AC: 22 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000225 AC: 25 AN: 1112012

Other (OTH) AF: 0.0000662 AC: 4 AN: 60396

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152208 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74406

African (AFR) AF: 0.0000241 AC: 1 AN: 41538

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000137 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.55	N
PhyloP100		4.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.33
Sift	Benign	0.082	T
Sift4G	Benign	0.071	T
Polyphen		0.0020	B
Vest4		0.58
MVP		0.77
MPC		1.1
ClinPred		0.034	T
GERP RS		4.6
Varity_R		0.16
gMVP		0.61
Mutation Taster		=81/19	polymorphism

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: rs187071817; hg19: chr7-98957207; COSMIC: COSV104368621; COSMIC: COSV104368621;