12-88505215-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000899.5(KITLG):​c.803G>C​(p.Arg268Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KITLG
NM_000899.5 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60
Variant links:
Genes affected
KITLG (HGNC:6343): (KIT ligand) This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KITLGNM_000899.5 linkc.803G>C p.Arg268Thr missense_variant Exon 9 of 10 ENST00000644744.1 NP_000890.1 P21583-1A0A024RBC0
KITLGNM_003994.6 linkc.719G>C p.Arg240Thr missense_variant Exon 8 of 9 NP_003985.2 P21583-2A0A024RBF5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KITLGENST00000644744.1 linkc.803G>C p.Arg268Thr missense_variant Exon 9 of 10 NM_000899.5 ENSP00000495951.1 P21583-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458884
Hom.:
0
Cov.:
28
AF XY:
0.00000138
AC XY:
1
AN XY:
725976
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.803G>C (p.R268T) alteration is located in exon 9 (coding exon 9) of the KITLG gene. This alteration results from a G to C substitution at nucleotide position 803, causing the arginine (R) at amino acid position 268 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.53
BayesDel_addAF
Pathogenic
0.36
D
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
26
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.44
T;.;T;.
Eigen
Uncertain
0.62
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Benign
0.72
D
LIST_S2
Uncertain
0.88
.;D;D;D
M_CAP
Benign
0.053
D
MetaRNN
Uncertain
0.53
D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Uncertain
2.2
M;.;M;.
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.8
.;N;N;.
REVEL
Benign
0.28
Sift
Uncertain
0.020
.;D;D;.
Sift4G
Benign
0.066
.;T;T;T
Polyphen
1.0
D;D;D;.
Vest4
0.47, 0.47, 0.40
MutPred
0.51
Gain of phosphorylation at R268 (P = 0.0559);.;Gain of phosphorylation at R268 (P = 0.0559);.;
MVP
0.68
MPC
0.93
ClinPred
0.97
D
GERP RS
5.3
Varity_R
0.11
gMVP
0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-88898992; API