Variant chr9-124875062-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030978.3(ARPC5L):c.310G>A(p.Gly104Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000753 in 1,461,760 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000075 ( 1 hom. )

Consequence

ARPC5L
NM_030978.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87

Variant links:

Genes affected

ARPC5L (HGNC:23366): (actin related protein 2/3 complex subunit 5 like) Predicted to enable actin filament binding activity. Predicted to be involved in Arp2/3 complex-mediated actin nucleation and cell migration. Located in extracellular exosome and focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ARPC5L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17496905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPC5L	NM_030978.3 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	5/6	ENST00000353214.6	NP_112240.1
ARPC5L	XM_047423941.1 linkuse as main transcript	c.154G>A	p.Gly52Ser	missense_variant	4/5		XP_047279897.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARPC5L	ENST00000353214.6 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	5/6	2	NM_030978.3	ENSP00000345361	P1
ARPC5L	ENST00000259477.6 linkuse as main transcript	c.310G>A	p.Gly104Ser	missense_variant	3/4	1		ENSP00000259477	P1
ARPC5L	ENST00000465124.1 linkuse as main transcript	n.1264G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727188

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jun 21, 2023

The c.310G>A (p.G104S) alteration is located in exon 3 (coding exon 3) of the ARPC5L gene. This alteration results from a G to A substitution at nucleotide position 310, causing the glycine (G) at amino acid position 104 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.048

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.13

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.49

N;N

REVEL

Uncertain

0.43

Sift

Benign

0.68

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.44

B;B

Vest4

0.25

MutPred

0.38

Gain of phosphorylation at G104 (P = 0.0658);Gain of phosphorylation at G104 (P = 0.0658);

MVP

0.49

MPC

1.3

ClinPred

0.92

GERP RS

6.1

Varity_R

0.31

gMVP

0.37

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