Variant 15-89903239-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_182616.4(ARPIN):c.649G>A(p.Asp217Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000321 in 1,614,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

ARPIN
NM_182616.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0114145875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ARPIN	NM_182616.4 linkuse as main transcript	c.649G>A	p.Asp217Asn	missense_variant	5/6	ENST00000357484.10
ARPIN-AP3S2	NM_001199058.2 linkuse as main transcript	c.649G>A	p.Asp217Asn	missense_variant	5/10
ARPIN	NM_001282380.2 linkuse as main transcript	c.361G>A	p.Asp121Asn	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARPIN	ENST00000357484.10 linkuse as main transcript	c.649G>A	p.Asp217Asn	missense_variant	5/6	1	NM_182616.4	P1	Q7Z6K5-1
ARPIN	ENST00000560096.1 linkuse as main transcript	c.310G>A	p.Asp104Asn	missense_variant	2/2	2
ARPIN	ENST00000460685.1 linkuse as main transcript	c.361G>A	p.Asp121Asn	missense_variant	5/6	2

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000365

AC:

AN:

249560

Hom.:

AF XY:

0.000391

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000397

Gnomad OTH exome

AF:

0.000824

GnomAD4 exome

AF:

0.000298

AC:

436

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000307

AC XY:

223

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000235

Gnomad4 OTH exome

AF:

0.000712

GnomAD4 genome

AF:

0.000538

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000522

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000487

Hom.:

Bravo

AF:

0.000797

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000476

AC:

ExAC

AF:

0.000289

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000652

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

May 30, 2024

The c.649G>A (p.D217N) alteration is located in exon 5 (coding exon 5) of the ARPIN gene. This alteration results from a G to A substitution at nucleotide position 649, causing the aspartic acid (D) at amino acid position 217 to be replaced by an asparagine (N). 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

-0.39

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

.;.;.;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;D;D;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.5

.;.;.;M;.

MutationTaster

Benign

1.0

D;D;D

PROVEAN

Benign

-0.52

N;N;N;N;D

REVEL

Benign

0.17

Sift

Uncertain

0.015

D;T;D;T;D

Sift4G

Uncertain

0.012

D;.;.;D;D

Polyphen

1.0

.;.;.;D;.

Vest4

0.45

MVP

0.46

MPC

0.053

ClinPred

0.050

GERP RS

5.7

Varity_R

0.31

gMVP

0.22

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

Other links and lift over