Variant 15-89903269-C-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_182616.4(ARPIN):c.619G>T(p.Gly207Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,614,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

ARPIN
NM_182616.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.407

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:38824): (ARPIN-AP3S2 readthrough) This locus represents naturally occurring read-through transcription between the neighboring C15orf38 (chromosome 15 open reading frame 38) and AP3S2 (adaptor-related protein complex 3, sigma 2 subunit) genes. The read-through transcript encodes a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Nov 2010]

ARPIN-AP3S2 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=0.09415418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPIN	NM_182616.4 link	c.619G>T	p.Gly207Trp	missense_variant	5/6	ENST00000357484.10	NP_872422.1	Q7Z6K5-1
ARPIN-AP3S2	NM_001199058.2 link	c.619G>T	p.Gly207Trp	missense_variant	5/10		NP_001185987.1	A0A0A6YYH1
ARPIN	NM_001282380.2 link	c.331G>T	p.Gly111Trp	missense_variant	5/6		NP_001269309.1	Q7Z6K5H0YMP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPIN	ENST00000357484.10 link	c.619G>T	p.Gly207Trp	missense_variant	5/6	1	NM_182616.4	ENSP00000350075.5		Q7Z6K5-1
ARPIN-AP3S2	ENST00000398333.7 link	c.619G>T	p.Gly207Trp	missense_variant	5/10	2		ENSP00000381377.3		A0A0A6YYH1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000761

AC:

AN:

249578

Hom.:

AF XY:

0.0000960

AC XY:

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

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:

0.0000477

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000316

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000578

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Dec 17, 2023

The c.619G>T (p.G207W) alteration is located in exon 5 (coding exon 5) of the ARPIN gene. This alteration results from a G to T substitution at nucleotide position 619, causing the glycine (G) at amino acid position 207 to be replaced by a tryptophan (W). 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

0.16

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.20

.;.;.;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.71

T;T;T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.094

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;.;.;M;.

PROVEAN

Benign

-1.4

N;N;N;N;N

REVEL

Benign

0.18

Sift

Uncertain

0.010

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;.;.;D;D

Polyphen

0.97

.;.;.;D;.

Vest4

0.53

MutPred

0.31

Loss of disorder (P = 0.0112);.;.;Loss of disorder (P = 0.0112);.;

MVP

0.20

MPC

0.28

ClinPred

0.090

GERP RS

1.7

Varity_R

0.041

gMVP

0.47

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