rs763865471

Variant names:

• chr19-55455276-C-A
• rs763865471
• NM_001136201.2:c.403G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-55455276-C-A
• chr19-55455276-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001136201.2(ISOC2):​c.403G>T​(p.Ala135Ser) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ISOC2 NM_001136201.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.70

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.821

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ISOC2	NM_001136201.2	c.403G>T	p.Ala135Ser	missense_variant	Exon 4 of 6	ENST00000425675.7	NP_001129673.1
ISOC2	NM_024710.3	c.451G>T	p.Ala151Ser	missense_variant	Exon 4 of 6		NP_078986.1
ISOC2	NM_001136202.2	c.193G>T	p.Ala65Ser	missense_variant	Exon 3 of 5		NP_001129674.1
ISOC2	XM_047439445.1	c.241G>T	p.Ala81Ser	missense_variant	Exon 3 of 5		XP_047295401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ISOC2	ENST00000425675.7	c.403G>T	p.Ala135Ser	missense_variant	Exon 4 of 6	1	NM_001136201.2	ENSP00000401726.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	.;T;.;T;T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Pathogenic	3.8	.;H;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.5	D;N;N;.;.
REVEL	Benign	0.21
Sift	Uncertain	0.017	D;D;T;.;.
Sift4G	Uncertain	0.015	D;D;D;.;.
Polyphen		0.77	P;B;B;.;.
Vest4		0.38
MutPred		0.80		.;Gain of disorder (P = 0.0166);.;Gain of disorder (P = 0.0166);Gain of disorder (P = 0.0166);
MVP		0.52
MPC		0.17
ClinPred		0.98	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.088
gMVP		0.68

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: rs763865471; hg19: chr19-55966643;