rs864309653

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_000899.5(KITLG):​c.286_303delAGTAATTATTCCATCATAinsT​(p.Ser96fs) variant causes a frameshift, synonymous change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. SNYSIID96*?) has been classified as Pathogenic. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

KITLG
NM_000899.5 frameshift, synonymous

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.61
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]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 12-88518757-TATGATGGAATAATTACT-A is Pathogenic according to our data. Variant chr12-88518757-TATGATGGAATAATTACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 218887.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KITLGNM_000899.5 linkuse as main transcriptc.286_303delAGTAATTATTCCATCATAinsT p.Ser96fs frameshift_variant, synonymous_variant 4/10 ENST00000644744.1 NP_000890.1 P21583-1A0A024RBC0
KITLGNM_003994.6 linkuse as main transcriptc.286_303delAGTAATTATTCCATCATAinsT p.Ser96fs frameshift_variant, synonymous_variant 4/9 NP_003985.2 P21583-2A0A024RBF5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KITLGENST00000644744.1 linkuse as main transcriptc.286_303delAGTAATTATTCCATCATAinsT p.Ser96fs frameshift_variant, synonymous_variant 4/10 NM_000899.5 ENSP00000495951.1 P21583-1

Frequencies

GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 69 Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 05, 2015- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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.

Other links and lift over

dbSNP: rs864309653; hg19: chr12-88912534; API