10-68988937-CA-C

Position:

• chr10-68988937-CA-C

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_015634.4(KIFBP):​c.108delA​(p.Lys36fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIFBP NM_015634.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 8.83

Genes affected

KIFBP (HGNC:23419): (kinesin family binding protein) This gene encodes a kinesin family member 1 binding protein that is characterized by two tetratrico peptide repeats. The encoded protein localizes to the mitochondria and may be involved in regulating transport of the mitochondria. Mutations in this gene are associated with Goldberg-Shprintzen megacolon syndrome. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Pathogenic. Variant got 12 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 10-68988937-CA-C is Pathogenic according to our data. Variant chr10-68988937-CA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2584999.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFBP	NM_015634.4	c.108delA	p.Lys36fs	frameshift_variant	1/7	ENST00000361983.7	NP_056449.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFBP	ENST00000361983.7	c.108delA	p.Lys36fs	frameshift_variant	1/7	1	NM_015634.4	ENSP00000354848.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Goldberg-Shprintzen syndrome Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Neuberg Centre For Genomic Medicine, NCGM

-

The frameshift deletion p.K36Nfs*57 in KIFBP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.K36Nfs*57 variant is novel (not in any individuals) in gnomAD exomes and is novel (not in any individuals) in 1000 Genomes. This variant has not been reported to the ClinVar database. This variant is predicted to cause loss of normal protein function through protein truncation caused a frameshift mutation. The frameshifted sequence continues 57 residues until a stop codon is reached. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. -

Computational scores

Source: dbNSFP v4.3

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: chr10-70748693;