chr15-89908303-G-A
Position:
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
NM_182616.4 missense
Scores
6
6
6
Clinical Significance
Conservation
PhyloP100: 7.86
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 |
---|---|---|---|---|---|---|---|
ARPIN | NM_182616.4 | c.278C>T | p.Thr93Met | missense_variant | 3/6 | ENST00000357484.10 | |
ARPIN-AP3S2 | NM_001199058.2 | c.278C>T | p.Thr93Met | missense_variant | 3/10 | ||
ARPIN | NM_001282380.2 | c.-11C>T | 5_prime_UTR_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ARPIN | ENST00000357484.10 | c.278C>T | p.Thr93Met | missense_variant | 3/6 | 1 | NM_182616.4 | P1 | |
ARPIN | ENST00000460685.1 | c.-11C>T | 5_prime_UTR_variant | 3/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
6
AN:
152218
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000721 AC: 18AN: 249504Hom.: 0 AF XY: 0.0000813 AC XY: 11AN XY: 135370
GnomAD3 exomes
AF:
AC:
18
AN:
249504
Hom.:
AF XY:
AC XY:
11
AN XY:
135370
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461872Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 727242
GnomAD4 exome
AF:
AC:
36
AN:
1461872
Hom.:
Cov.:
30
AF XY:
AC XY:
25
AN XY:
727242
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74362
GnomAD4 genome
AF:
AC:
6
AN:
152218
Hom.:
Cov.:
33
AF XY:
AC XY:
6
AN XY:
74362
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
6
Asia WGS
AF:
AC:
3
AN:
3478
EpiCase
AF:
EpiControl
AF:
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 17, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D;D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
0.99
.;D
Vest4
MutPred
Loss of phosphorylation at T93 (P = 0.0583);Loss of phosphorylation at T93 (P = 0.0583);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at