rs1085307110

Variant names:

• chr3-134650909-C-CATGTCGATAGATACAGCACATGTCGATA
• rs1085307110
• NM_178554.6:c.51_52insTATCGACATGTGCTGTATCTATCGACAT

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_178554.6(KY):​c.51_52insTATCGACATGTGCTGTATCTATCGACAT​(p.Val18TyrfsTer56) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KY NM_178554.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.257

Genes affected

KY (HGNC:26576): (kyphoscoliosis peptidase) The protein encoded by this gene belongs to the transglutaminase-like superfamily. The protein is involved in the function, maturation and stabilization of the neuromuscular junction and may be required for normal muscle growth. Mutations in this gene are associated with myopathy, myofibrillar, 7. [provided by RefSeq, Apr 2017]

ENSG00000288700 (HGNC:):

CEP63 (HGNC:25815): (centrosomal protein 63) This gene encodes a protein with six coiled-coil domains. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. Several alternatively spliced transcript variants have been found, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.974 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 3-134650909-C-CATGTCGATAGATACAGCACATGTCGATA is Pathogenic according to our data. Variant chr3-134650909-C-CATGTCGATAGATACAGCACATGTCGATA is described in ClinVar as [Pathogenic]. Clinvar id is 402246.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KY	NM_178554.6	c.51_52insTATCGACATGTGCTGTATCTATCGACAT	p.Val18TyrfsTer56	frameshift_variant	Exon 1 of 11	ENST00000423778.7	NP_848649.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KY	ENST00000423778.7	c.51_52insTATCGACATGTGCTGTATCTATCGACAT	p.Val18TyrfsTer56	frameshift_variant	Exon 1 of 11	5	NM_178554.6	ENSP00000397598.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Hereditary spastic paraplegia Pathogenic:1

Feb 14, 2017

The Morris Kahn Laboratory of Human Genetics, Ben-Gurion University of the Negev

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

Variant segregates within affected families with a LOD score of 9.02 , more than 12 patients -

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: rs1085307110; hg19: chr3-134369751;