12-64212659-C-T

Position:

• chr12-64212659-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.521+3019G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,148 control chromosomes in the GnomAD database, including 43,408 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 0.75 (43408 hom., cov: 33)
• Consequence: KICS2 NM_152440.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KICS2	NM_152440.5	c.521+3019G>A		intron_variant		ENST00000398055.8	NP_689653.4
KICS2	NM_001300940.2	c.521+3019G>A		intron_variant			NP_001287869.2
KICS2	NM_001300941.2	c.362+3019G>A		intron_variant			NP_001287870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KICS2	ENST00000398055.8	c.521+3019G>A		intron_variant		1	NM_152440.5	ENSP00000381132.4
KICS2	ENST00000311915.12	c.521+3019G>A		intron_variant		1		ENSP00000311486.8
KICS2	ENST00000544871.1	c.362+3019G>A		intron_variant		2		ENSP00000445481.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114114 AN: 152030 Hom.: 43405 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.794

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.750 AC: 114161 AN: 152148 Hom.: 43408 Cov.: 33 AF XY: 0.751 AC XY: 55880 AN XY: 74360

Gnomad4 AFR AF: 0.623

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.943

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.770

Gnomad4 NFE AF: 0.794

Gnomad4 OTH AF: 0.791

Alfa AF: 0.740 Hom.: 4237

Bravo AF: 0.746

Asia WGS AF: 0.897 AC: 3119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.62
DANN	Benign	0.55

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: rs790006; hg19: chr12-64606439;