Variant 15-89903917-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182616.4(ARPIN):c.368C>T(p.Pro123Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,958 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: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ARPIN
NM_182616.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.27

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.30776498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPIN	NM_182616.4 link	c.368C>T	p.Pro123Leu	missense_variant	4/6	ENST00000357484.10	NP_872422.1	Q7Z6K5-1
ARPIN-AP3S2	NM_001199058.2 link	c.368C>T	p.Pro123Leu	missense_variant	4/10		NP_001185987.1	A0A0A6YYH1
ARPIN	NM_001282380.2 link	c.80C>T	p.Pro27Leu	missense_variant	4/6		NP_001269309.1	Q7Z6K5H0YMP5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPIN	ENST00000357484.10 link	c.368C>T	p.Pro123Leu	missense_variant	4/6	1	NM_182616.4	ENSP00000350075.5		Q7Z6K5-1
ARPIN-AP3S2	ENST00000398333.7 link	c.368C>T	p.Pro123Leu	missense_variant	4/10	2		ENSP00000381377.3		A0A0A6YYH1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248778

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460958

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726820

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

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

Jan 09, 2024

The c.368C>T (p.P123L) alteration is located in exon 4 (coding exon 4) of the ARPIN gene. This alteration results from a C to T substitution at nucleotide position 368, causing the proline (P) at amino acid position 123 to be replaced by a leucine (L). 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

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

.;.;T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.3

.;.;M;.

PROVEAN

Benign

-1.5

N;N;D;D

REVEL

Benign

0.091

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.0050

D;.;D;T

Polyphen

0.77

.;.;P;.

Vest4

0.50

MutPred

0.47

Loss of loop (P = 0.0128);.;Loss of loop (P = 0.0128);.;

MVP

0.54

MPC

0.11

ClinPred

0.74

GERP RS

5.1

Varity_R

0.075

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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