3-9793140-C-T

Position:

chr3-9793140-C-T

Variant summary

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

The NM_001198780.3(ARPC4):c.19C>T(p.Pro7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000175 in 1,541,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ARPC4
NM_001198780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.100

Variant links:

Genes affected

ARPC4 (HGNC:707): (actin related protein 2/3 complex subunit 4) This gene encodes one of seven subunits of the human Arp2/3 protein complex. This complex controls actin polymerization in cells and has been conserved throughout eukaryotic evolution. This gene encodes the p20 subunit, which is necessary for actin nucleation and high-affinity binding to F-actin. Alternative splicing results in multiple transcript variants. Naturally occurring read-through transcription exists between this gene and the downstream tubulin tyrosine ligase-like family, member 3 (TTLL3), which results in the production of a fusion protein. [provided by RefSeq, Nov 2010]

ARPC4 links:

ARPC4-TTLL3 (HGNC:38830): (ARPC4-TTLL3 readthrough) This locus represents naturally occurring read-through transcription between the neighboring ARPC4 (actin related protein 2/3 complex, subunit 4) and TTLL3 (tubulin tyrosine ligase-like family, member 3) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ARPC4-TTLL3 links:

ARPC4 (HGNC:):

ARPC4 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=0.07000637).

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC4	NM_005718.5 linkuse as main transcript	c.3+16C>T		intron_variant		ENST00000397261.8	NP_005709.1	P59998-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC4	ENST00000397261.8 linkuse as main transcript	c.3+16C>T		intron_variant		1	NM_005718.5	ENSP00000380431.2		P59998-1
ARPC4-TTLL3	ENST00000397256.5 linkuse as main transcript	c.3+16C>T		intron_variant		5		ENSP00000380427.1		A0A0A6YYG9

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000701

AC:

AN:

142600

Hom.:

AF XY:

0.0000130

AC XY:

AN XY:

77170

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:

0.00

Gnomad NFE exome

AF:

0.0000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000180

AC:

AN:

1388822

Hom.:

Cov.:

AF XY:

0.0000175

AC XY:

AN XY:

684300

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:

0.00

Gnomad4 NFE exome

AF:

0.0000233

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.19C>T (p.P7S) alteration is located in exon 1 (coding exon 1) of the ARPC4 gene. This alteration results from a C to T substitution at nucleotide position 19, causing the proline (P) at amino acid position 7 to be replaced by a serine (S). 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

BayesDel_addAF

Benign

-0.033

BayesDel_noAF

Benign

-0.28

CADD

Benign

9.4

DANN

Benign

0.84

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.39

M_CAP

Benign

0.012

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.15

REVEL

Benign

0.049

Sift

Uncertain

0.020

Sift4G

Benign

0.47

Vest4

0.16

MutPred

0.080

Gain of phosphorylation at P7 (P = 0.0123);

MVP

0.13

MPC

1.1

ClinPred

0.34

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

gMVP

0.092

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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