Variant 7-99388183-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5

The NM_005720.4(ARPC1B):c.314C>T(p.Ala105Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ARPC1B
NM_005720.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

ARPC1B (HGNC:704): (actin related protein 2/3 complex subunit 1B) 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 ARPC1A. 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. This protein also has a role in centrosomal homeostasis by being an activator and substrate of the Aurora A kinase. [provided by RefSeq, Mar 2011]

ARPC1B links:

ENSG00000284292 (HGNC:):

ENSG00000284292 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-99388183-C-T is Pathogenic according to our data. Variant chr7-99388183-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 444878.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC1B	NM_005720.4 link	c.314C>T	p.Ala105Val	missense_variant	4/10	ENST00000646101.2	NP_005711.1	O15143A4D275
ARPC1B	XM_024446628.2 link	c.314C>T	p.Ala105Val	missense_variant	4/10		XP_024302396.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPC1B	ENST00000646101.2 link	c.314C>T	p.Ala105Val	missense_variant	4/10		NM_005720.4	ENSP00000496599.1		O15143
ENSG00000284292	ENST00000638617.1 link	c.1310C>T	p.Ala437Val	missense_variant	11/17	5		ENSP00000491073.1		A0A1W2PNV4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727238

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:

0.00000719

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Platelet abnormalities with eosinophilia and immune-mediated inflammatory disease

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.058

.;T;T;T;T;.;T;T;T;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.87

D;D;.;.;.;D;.;.;.;.;D

M_CAP

Benign

0.043

MetaRNN

Uncertain

0.53

D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.4

.;.;L;L;L;.;L;L;L;L;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.0

.;D;.;D;D;D;D;D;D;D;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

.;D;.;D;D;D;D;D;D;D;.

Sift4G

Uncertain

0.0020

.;D;.;D;D;D;D;D;D;D;.

Polyphen

0.89

.;.;P;P;P;.;P;P;P;P;P

Vest4

0.47, 0.47

MutPred

0.68

.;Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);Gain of methylation at K110 (P = 0.0849);

MVP

0.82

MPC

0.50

ClinPred

0.98

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.74

gMVP

0.34

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

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

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