rs1042477302

Variant names:

• chr19-55455009-C-A
• rs1042477302
• NM_001136201.2:c.517G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55455009-C-A
• chr19-55455009-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136201.2(ISOC2):​c.517G>T​(p.Val173Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: ISOC2 NM_001136201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

Genes affected

ISOC2 (HGNC:26278): (isochorismatase domain containing 2) Involved in protein destabilization. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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=0.11603922).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISOC2	NM_001136201.2	c.517G>T	p.Val173Phe	missense_variant	Exon 5 of 6	ENST00000425675.7	NP_001129673.1
ISOC2	NM_024710.3	c.565G>T	p.Val189Phe	missense_variant	Exon 5 of 6		NP_078986.1
ISOC2	NM_001136202.2	c.307G>T	p.Val103Phe	missense_variant	Exon 4 of 5		NP_001129674.1
ISOC2	XM_047439445.1	c.355G>T	p.Val119Phe	missense_variant	Exon 4 of 5		XP_047295401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISOC2	ENST00000425675.7	c.517G>T	p.Val173Phe	missense_variant	Exon 5 of 6	1	NM_001136201.2	ENSP00000401726.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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 Cov.: 34

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152094 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74298

Gnomad4 AFR AF: 0.0000242

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: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	.;T;.;T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.95	D;T;T;D;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	.;N;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.99	N;N;N;.;.
REVEL	Benign	0.040
Sift	Benign	0.049	D;D;D;.;.
Sift4G	Uncertain	0.042	D;D;D;.;.
Polyphen		0.28	B;B;B;.;.
Vest4		0.30
MutPred		0.32		.;Gain of solvent accessibility (P = 0.1185);.;Gain of solvent accessibility (P = 0.1185);Gain of solvent accessibility (P = 0.1185);
MVP		0.19
MPC		0.14
ClinPred		0.23	T
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.046
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs1042477302; hg19: chr19-55966376;