12-64203799-C-T

Position:

• chr12-64203799-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152440.5(KICS2):​c.522-9141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,082 control chromosomes in the GnomAD database, including 17,591 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (17591 hom., cov: 33)
• Consequence: KICS2 NM_152440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KICS2	NM_152440.5	c.522-9141G>A		intron_variant		ENST00000398055.8	NP_689653.4
KICS2	NM_001300940.2	c.522-9141G>A		intron_variant			NP_001287869.2
KICS2	NM_001300941.2	c.363-9141G>A		intron_variant			NP_001287870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KICS2	ENST00000398055.8	c.522-9141G>A		intron_variant		1	NM_152440.5	ENSP00000381132.4
KICS2	ENST00000311915.12	c.522-9141G>A		intron_variant		1		ENSP00000311486.8
KICS2	ENST00000544871.1	c.363-9141G>A		intron_variant		2		ENSP00000445481.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72599 AN: 151966 Hom.: 17586 Cov.: 33

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.478 AC: 72628 AN: 152082 Hom.: 17591 Cov.: 33 AF XY: 0.476 AC XY: 35362 AN XY: 74332

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.500

Alfa AF: 0.498 Hom.: 2905

Bravo AF: 0.479

Asia WGS AF: 0.510 AC: 1776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.72

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: rs1695105; hg19: chr12-64597579;