rs864309653

Variant names:

• chr12-88518757-TATGATGGAATAATTACT-A
• rs864309653
• NM_000899.5:c.286_303delAGTAATTATTCCATCATAinsT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

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
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 5.61

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]

ACMG classification

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 rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift_variant, synonymous_variant	Exon 4 of 10	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift_variant, synonymous_variant	Exon 4 of 9		NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.286_303delAGTAATTATTCCATCATAinsT	p.Ser96fs	frameshift_variant, synonymous_variant	Exon 4 of 10		NM_000899.5	ENSP00000495951.1

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: no classifications from unflagged records

Submissions summary: Pathogenic:1

Revision: no classifications from unflagged records

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 69 Pathogenic:1

Nov 05, 2015

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs864309653; hg19: chr12-88912534;