5-129095029-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016048.2(ISOC1):​c.263C>T​(p.Ala88Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,597,856 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 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ISOC1
NM_016048.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58
Variant links:
Genes affected
ISOC1 (HGNC:24254): (isochorismatase domain containing 1) Predicted to be located in peroxisome. Predicted to be active in cytoplasm. [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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0841409).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ISOC1NM_016048.2 linkc.263C>T p.Ala88Val missense_variant Exon 1 of 5 ENST00000173527.6 NP_057132.2 Q96CN7
LOC124901060XR_007058926.1 linkn.602G>A non_coding_transcript_exon_variant Exon 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ISOC1ENST00000173527.6 linkc.263C>T p.Ala88Val missense_variant Exon 1 of 5 1 NM_016048.2 ENSP00000173527.5 Q96CN7
ISOC1ENST00000514194.5 linkc.263C>T p.Ala88Val missense_variant Exon 1 of 3 3 ENSP00000421273.1 D6RGE2

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152234
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000723
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1445622
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
718820
show subpopulations
Gnomad4 AFR exome
AF:
0.0000306
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152234
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0000723
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 20, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.263C>T (p.A88V) alteration is located in exon 1 (coding exon 1) of the ISOC1 gene. This alteration results from a C to T substitution at nucleotide position 263, causing the alanine (A) at amino acid position 88 to be replaced by a valine (V). 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
0.069
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0038
T;T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.73
T;T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.084
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-0.26
N;N
REVEL
Benign
0.021
Sift
Benign
0.21
T;T
Sift4G
Benign
0.88
T;T
Polyphen
0.0
.;B
Vest4
0.062
MutPred
0.34
Loss of catalytic residue at A88 (P = 0.0376);Loss of catalytic residue at A88 (P = 0.0376);
MVP
0.29
MPC
0.27
ClinPred
0.092
T
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.070
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs904567424; hg19: chr5-128430722; API