rs904567424

Variant summary

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

The NM_016048.2(ISOC1):​c.263C>G​(p.Ala88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,445,622 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A88V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)
Exomes š‘“: 0.0000035 ( 0 hom. )

Consequence

ISOC1
NM_016048.2 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

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=0.1003319).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ISOC1NM_016048.2 linkc.263C>G p.Ala88Gly missense_variant Exon 1 of 5 ENST00000173527.6 NP_057132.2 Q96CN7
LOC124901060XR_007058926.1 linkn.602G>C 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>G p.Ala88Gly missense_variant Exon 1 of 5 1 NM_016048.2 ENSP00000173527.5 Q96CN7
ISOC1ENST00000514194.5 linkc.263C>G p.Ala88Gly missense_variant Exon 1 of 3 3 ENSP00000421273.1 D6RGE2

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000346
AC:
5
AN:
1445622
Hom.:
0
Cov.:
30
AF XY:
0.00000278
AC XY:
2
AN XY:
718820
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:
0.0000473
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.015
T;T
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.77
T;T
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
.;N
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.73
N;N
REVEL
Benign
0.038
Sift
Benign
0.059
T;T
Sift4G
Benign
0.20
T;T
Polyphen
0.0
.;B
Vest4
0.12
MutPred
0.29
Loss of sheet (P = 0.0126);Loss of sheet (P = 0.0126);
MVP
0.28
MPC
0.28
ClinPred
0.29
T
GERP RS
1.4
Varity_R
0.10
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-128430722; API