Variant chr15-89903379-T-C 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_182616.4(ARPIN):c.509A>G(p.Asp170Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ARPIN
NM_182616.4 missense, splice_region

Scores

Splicing: ADA: 0.0005239

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Variant links:

Genes affected

ARPIN (HGNC:28782): (actin related protein 2/3 complex inhibitor) Involved in directional locomotion; negative regulation of cell migration; and negative regulation of cellular component organization. Predicted to be located in lamellipodium. [provided by Alliance of Genome Resources, Apr 2022]

ARPIN links:

ARPIN-AP3S2 (HGNC:):

ARPIN-AP3S2 links:

Genome browser will be placed here

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=0.24428508).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARPIN	NM_182616.4 linkuse as main transcript	c.509A>G	p.Asp170Gly	missense_variant, splice_region_variant	5/6	ENST00000357484.10
ARPIN-AP3S2	NM_001199058.2 linkuse as main transcript	c.509A>G	p.Asp170Gly	missense_variant, splice_region_variant	5/10
ARPIN	NM_001282380.2 linkuse as main transcript	c.221A>G	p.Asp74Gly	missense_variant, splice_region_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARPIN	ENST00000357484.10 linkuse as main transcript	c.509A>G	p.Asp170Gly	missense_variant, splice_region_variant	5/6	1	NM_182616.4	P1	Q7Z6K5-1
ARPIN	ENST00000560096.1 linkuse as main transcript	c.170A>G	p.Asp57Gly	missense_variant, splice_region_variant	2/2	2
ARPIN	ENST00000460685.1 linkuse as main transcript	c.221A>G	p.Asp74Gly	missense_variant, splice_region_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727234

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74338

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Nov 14, 2023

The c.509A>G (p.D170G) alteration is located in exon 5 (coding exon 5) of the ARPIN gene. This alteration results from a A to G substitution at nucleotide position 509, causing the aspartic acid (D) at amino acid position 170 to be replaced by a glycine (G). 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

0.14

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.21

.;.;T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.64

T;T;T;T

M_CAP

Benign

0.0036

MetaRNN

Benign

0.24

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.11

.;.;N;.

MutationTaster

Benign

0.70

N;N;N

PROVEAN

Benign

-0.070

N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.17

T;T;T;T

Sift4G

Benign

0.22

T;.;T;T

Polyphen

0.0

.;.;B;.

Vest4

0.26

MutPred

0.52

Gain of sheet (P = 0.0149);.;Gain of sheet (P = 0.0149);.;

MVP

0.18

MPC

0.13

ClinPred

0.38

GERP RS

4.3

Varity_R

0.10

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00052

dbscSNV1_RF

Benign

0.020

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

Other links and lift over