rs730882157
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3PP5
The NM_000899.5(KITLG):c.100A>C(p.Thr34Pro) variant causes a missense change. 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
KITLG
NM_000899.5 missense
NM_000899.5 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 4.80
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM1
In a disulfide_bond (size 85) in uniprot entity SCF_HUMAN there are 4 pathogenic changes around while only 1 benign (80%) in NM_000899.5
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.838
PP5
Variant 12-88545781-T-G is Pathogenic according to our data. Variant chr12-88545781-T-G is described in ClinVar as [Pathogenic]. Clinvar id is 183169.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr12-88545781-T-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KITLG | NM_000899.5 | c.100A>C | p.Thr34Pro | missense_variant | 2/10 | ENST00000644744.1 | NP_000890.1 | |
KITLG | NM_003994.6 | c.100A>C | p.Thr34Pro | missense_variant | 2/9 | NP_003985.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KITLG | ENST00000644744.1 | c.100A>C | p.Thr34Pro | missense_variant | 2/10 | NM_000899.5 | ENSP00000495951.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hyperpigmentation with or without hypopigmentation, familial progressive Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2011 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
.;D;D
REVEL
Uncertain
Sift
Pathogenic
.;D;D
Sift4G
Uncertain
.;D;T
Polyphen
B;B;B
Vest4
0.89, 0.93
MutPred
Loss of glycosylation at T34 (P = 0.0702);Loss of glycosylation at T34 (P = 0.0702);Loss of glycosylation at T34 (P = 0.0702);
MVP
0.91
MPC
0.88
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at