chr15-89908303-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_182616.4(ARPIN):​c.278C>T​(p.Thr93Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000026 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ARPIN
NM_182616.4 missense

Scores

6
6
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.86
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.924

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ARPINNM_182616.4 linkuse as main transcriptc.278C>T p.Thr93Met missense_variant 3/6 ENST00000357484.10
ARPIN-AP3S2NM_001199058.2 linkuse as main transcriptc.278C>T p.Thr93Met missense_variant 3/10
ARPINNM_001282380.2 linkuse as main transcriptc.-11C>T 5_prime_UTR_variant 3/6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ARPINENST00000357484.10 linkuse as main transcriptc.278C>T p.Thr93Met missense_variant 3/61 NM_182616.4 P1Q7Z6K5-1
ARPINENST00000460685.1 linkuse as main transcriptc.-11C>T 5_prime_UTR_variant 3/62

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000721
AC:
18
AN:
249504
Hom.:
0
AF XY:
0.0000813
AC XY:
11
AN XY:
135370
show subpopulations
Gnomad AFR exome
AF:
0.0000645
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.000167
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000246
AC:
36
AN:
1461872
Hom.:
0
Cov.:
30
AF XY:
0.0000344
AC XY:
25
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000629
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152218
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000495
AC:
6
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsMay 17, 2023The c.278C>T (p.T93M) alteration is located in exon 3 (coding exon 3) of the ARPIN gene. This alteration results from a C to T substitution at nucleotide position 278, causing the threonine (T) at amino acid position 93 to be replaced by a methionine (M). 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
0.21
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.73
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;D
M_CAP
Benign
0.071
D
MetaRNN
Pathogenic
0.92
D;D
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.5
.;M
MutationTaster
Benign
1.0
D;D;D
PROVEAN
Uncertain
-2.6
D;D
REVEL
Uncertain
0.47
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.99
.;D
Vest4
0.90
MutPred
0.83
Loss of phosphorylation at T93 (P = 0.0583);Loss of phosphorylation at T93 (P = 0.0583);
MVP
0.70
MPC
0.35
ClinPred
0.47
T
GERP RS
5.4
Varity_R
0.47
gMVP
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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.

Other links and lift over

dbSNP: rs373434670; hg19: chr15-90451535; API