Variant 12-64215782-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000398055.8(KICS2):c.417A>G(p.Ile139Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,614,098 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.014 ( 51 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 55 hom. )

Consequence

KICS2
ENST00000398055.8 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0250

Variant links:

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]

KICS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009997815).

BP6

Variant 12-64215782-T-C is Benign according to our data. Variant chr12-64215782-T-C is described in ClinVar as [Benign]. Clinvar id is 776729.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.014 (2134/152272) while in subpopulation AFR AF= 0.0488 (2026/41544). AF 95% confidence interval is 0.047. There are 51 homozygotes in gnomad4. There are 985 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KICS2	NM_152440.5 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	2/3	ENST00000398055.8	NP_689653.4
KICS2	NM_001300940.2 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	2/4		NP_001287869.2
KICS2	NM_001300941.2 linkuse as main transcript	c.258A>G	p.Ile86Met	missense_variant	2/3		NP_001287870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KICS2	ENST00000398055.8 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	2/3	1	NM_152440.5	ENSP00000381132	P1
KICS2	ENST00000311915.12 linkuse as main transcript	c.417A>G	p.Ile139Met	missense_variant	2/4	1		ENSP00000311486
KICS2	ENST00000544871.1 linkuse as main transcript	c.258A>G	p.Ile86Met	missense_variant	2/3	2		ENSP00000445481

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2131

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0488

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00510

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00670

GnomAD4 exome

AF:

0.00138

AC:

2012

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

847

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0500

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000629

Gnomad4 OTH exome

AF:

0.00255

GnomAD4 genome

AF:

0.0140

AC:

2134

AN:

152272

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

985

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0488

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.0159

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.064

DEOGEN2

Benign

0.0058

.;.;T

LIST_S2

Benign

0.70

T;.;T

MetaRNN

Benign

0.010

T;T;T

Sift4G

Benign

0.24

T;T;T

Vest4

0.24

gMVP

0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over