rs904567424

Variant names:

• chr5-129095029-C-G
• NM_016048.2:c.263C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-129095029-C-G
• chr5-129095029-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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 𝑓: 0.0000035 (0 hom.)
• Consequence: ISOC1 NM_016048.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.58

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]

LOC124901060 (HGNC:):

ACMG classification

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
ISOC1	NM_016048.2	c.263C>G	p.Ala88Gly	missense_variant	Exon 1 of 5	ENST00000173527.6	NP_057132.2
LOC124901060	XR_007058926.1	n.602G>C		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	c.263C>G	p.Ala88Gly	missense_variant	Exon 1 of 5	1	NM_016048.2	ENSP00000173527.5
ISOC1	ENST00000514194.5	c.263C>G	p.Ala88Gly	missense_variant	Exon 1 of 3	3		ENSP00000421273.1

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

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;