rs1248819585

Variant names:

• chr5-129094944-G-C
• rs1248819585
• NM_016048.2:c.178G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-129094944-G-C
• chr5-129094944-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016048.2(ISOC1):​c.178G>C​(p.Asp60His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,459,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. D60Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ISOC1 NM_016048.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.75

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31342983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISOC1	NM_016048.2	c.178G>C	p.Asp60His	missense_variant	Exon 1 of 5	ENST00000173527.6	NP_057132.2
LOC124901060	XR_007058926.1	n.687C>G		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.178G>C	p.Asp60His	missense_variant	Exon 1 of 5	1	NM_016048.2	ENSP00000173527.5
ISOC1	ENST00000514194.5	c.178G>C	p.Asp60His	missense_variant	Exon 1 of 3	3		ENSP00000421273.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459824 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726280

African (AFR) AF: 0.00 AC: 0 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86100

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111808

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	0.0058	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0080	T;T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.76	T;T
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.34	.;N
PhyloP100		3.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.43	N;N
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.99	.;D
Vest4		0.28
MutPred		0.22		Loss of stability (P = 0.0659);Loss of stability (P = 0.0659);
MVP		0.56
MPC		0.51
ClinPred		0.86	D
GERP RS		4.0
PromoterAI		-0.054	Neutral
Varity_R		0.44
gMVP		0.42
Mutation Taster		=83/17	polymorphism

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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Other links and lift over

dbSNP: rs1248819585; hg19: chr5-128430637;