Variant 3-9801666-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005718.5(ARPC4):c.240T>G(p.Asp80Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00094 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ARPC4
NM_005718.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.500

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC4	NM_005718.5 linkuse as main transcript	c.240T>G	p.Asp80Glu	missense_variant	4/6	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.240T>G	p.Asp80Glu	missense_variant	4/6	1	NM_005718.5	ENSP00000380431.2		P59998-1
ARPC4-TTLL3	ENST00000397256.5 linkuse as main transcript	c.240T>G	p.Asp80Glu	missense_variant	4/12	5		ENSP00000380427.1		A0A0A6YYG9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152126

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000940

AC:

1357

AN:

1444004

Hom.:

Cov.:

AF XY:

0.000856

AC XY:

615

AN XY:

718188

show subpopulations

Gnomad4 AFR exome

AF:

0.000634

Gnomad4 AMR exome

AF:

0.0000908

Gnomad4 ASJ exome

AF:

0.000508

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000377

Gnomad4 FIN exome

AF:

0.0000754

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.000736

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000131

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Oct 03, 2023

The c.297T>G (p.D99E) alteration is located in exon 4 (coding exon 4) of the ARPC4 gene. This alteration results from a T to G substitution at nucleotide position 297, causing the aspartic acid (D) at amino acid position 99 to be replaced by a glutamic acid (E). 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

1.0

BayesDel_addAF

Benign

0.0010

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.43

T;.;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.86

D;D;D

M_CAP

Benign

0.063

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.6

H;.;.

PROVEAN

Uncertain

-3.8

D;D;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.023

D;D;T

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.72

MutPred

0.83

Gain of helix (P = 0.0496);.;Gain of helix (P = 0.0496);

MVP

0.58

MPC

2.1, 2.2

ClinPred

0.99

GERP RS

3.6

Varity_R

0.28

gMVP

0.78

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over