Genetic Variant NM_016048.2:c.29C>T (chr5-129094795-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016048.2(ISOC1):c.29C>T(p.Ala10Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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. A10E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ISOC1
NM_016048.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

0 publications found

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]

ISOC1 links:

LOC124901060 (HGNC:):

LOC124901060 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15018308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISOC1	NM_016048.2 link	c.29C>T	p.Ala10Val	missense_variant	Exon 1 of 5	ENST00000173527.6	NP_057132.2	Q96CN7
LOC124901060	XR_007058926.1 link	n.836G>A		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISOC1	ENST00000173527.6 link	c.29C>T	p.Ala10Val	missense_variant	Exon 1 of 5	1	NM_016048.2	ENSP00000173527.5		Q96CN7
ISOC1	ENST00000514194.5 link	c.29C>T	p.Ala10Val	missense_variant	Exon 1 of 3	3		ENSP00000421273.1		D6RGE2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1370930

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676182

African (AFR)

AF:

0.00

AC:

AN:

29674

American (AMR)

AF:

0.00

AC:

AN:

34018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24670

East Asian (EAS)

AF:

0.00

AC:

AN:

33810

South Asian (SAS)

AF:

0.00

AC:

AN:

77208

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37652

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1072534

Other (OTH)

AF:

0.00

AC:

AN:

57158

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0085

T;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.51

T;T

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.15

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PhyloP100

1.5

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.10

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.018

.;B

Vest4

0.16

MutPred

0.30

Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);

MVP

0.18

MPC

0.27

ClinPred

0.16

GERP RS

2.8

PromoterAI

0.070

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.35

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over