Variant 7-99365918-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006409.4(ARPC1A):c.1102C>T(p.Arg368Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000965 in 1,574,466 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 (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

ARPC1A
NM_006409.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.96

Variant links:

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]

ARPC1A links:

ENSG00000284292 (HGNC:):

ENSG00000284292 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1705778).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC1A	NM_006409.4 linkuse as main transcript	c.1102C>T	p.Arg368Trp	missense_variant	10/10	ENST00000262942.10	NP_006400.2	Q92747-1V9HVZ6
ARPC1A	NM_001190996.2 linkuse as main transcript	c.1060C>T	p.Arg354Trp	missense_variant	10/10		NP_001177925.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC1A	ENST00000262942.10 linkuse as main transcript	c.1102C>T	p.Arg368Trp	missense_variant	10/10	1	NM_006409.4	ENSP00000262942.5		Q92747-1
ENSG00000284292	ENST00000638617.1 linkuse as main transcript	c.983+6180C>T		intron_variant		5		ENSP00000491073.1		A0A1W2PNV4

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000785

AC:

AN:

190962

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

101862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000475

Gnomad NFE exome

AF:

0.0000878

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000984

AC:

140

AN:

1422124

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

703310

show subpopulations

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:

0.000339

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.0000850

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152342

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000673

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.1102C>T (p.R368W) alteration is located in exon 10 (coding exon 9) of the ARPC1A gene. This alteration results from a C to T substitution at nucleotide position 1102, causing the arginine (R) at amino acid position 368 to be replaced by a tryptophan (W). 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.23

Eigen

Benign

0.047

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.062

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.31

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0020

Polyphen

0.0010

Vest4

0.48

MVP

0.65

MPC

0.87

ClinPred

0.37

GERP RS

4.6

Varity_R

0.63

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over