12-64222231-C-A

Variant names:

• chr12-64222231-C-A
• NM_152440.5:c.7G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_152440.5(KICS2):​c.7G>T​(p.Glu3*) variant causes a stop gained 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KICS2 NM_152440.5 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.22

Genes affected

KICS2 (HGNC:26517): (KICSTOR subunit 2) Involved in cellular response to starvation; negative regulation of TORC1 signaling; and protein localization to lysosome. Located in intercellular bridge and lysosome. Part of KICSTOR complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000243024 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-64222231-C-A is Pathogenic according to our data. Variant chr12-64222231-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 3747841.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KICS2	NM_152440.5	c.7G>T	p.Glu3*	stop_gained	Exon 1 of 3	ENST00000398055.8	NP_689653.4
KICS2	NM_001300940.2	c.7G>T	p.Glu3*	stop_gained	Exon 1 of 4		NP_001287869.2
KICS2	NM_001300941.2	c.7G>T	p.Glu3*	stop_gained	Exon 1 of 3		NP_001287870.2
LOC124902952	XR_007063347.1	n.-118C>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KICS2	ENST00000398055.8	c.7G>T	p.Glu3*	stop_gained	Exon 1 of 3	1	NM_152440.5	ENSP00000381132.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual developmental disorder, autosomal recessive 83 Pathogenic:1

Feb 19, 2025

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.50
CADD	Pathogenic	39
DANN	Uncertain	1.0
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.78	D
Vest4		0.35
GERP RS		4.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-64616011;