20-16312355-CAG-C

Position:

• chr20-16312355-CAG-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024704.5(KIF16B):​c.3773_3774delCT​(p.Ala1258fs) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF16B NM_024704.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.24

Genes affected

KIF16B (HGNC:15869): (kinesin family member 16B) The protein encoded by this gene is a kinesin-like protein that may be involved in intracellular trafficking. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF16B	NM_024704.5	c.3773_3774delCT	p.Ala1258fs	frameshift_variant	25/26	ENST00000354981.7	NP_078980.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF16B	ENST00000354981.7	c.3773_3774delCT	p.Ala1258fs	frameshift_variant	25/26	1	NM_024704.5	ENSP00000347076.2
KIF16B	ENST00000636835.1	c.3620_3621delCT	p.Ala1207fs	frameshift_variant	24/25	1		ENSP00000489838.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Muscular atrophy Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Institute of Human Genetics, University of Goettingen

Mar 17, 2021

The variant c.3773_3774del (p.(Ala1258Glyfs*41)) in exon 25 of the KIF16B-gene is not found in the gnomAD database. This variation creates a frame shift starting at codon Ala1258. The new reading frame ends in a STOP codon at position 41. Pathogenic computational verdict based on 1 pathogenic prediction from phyloP vs no benign predictions. This variant was found in an affected individual but was not found in his affected son in our clinic, thus we classify this variant as a Variant of uncertain significance. ACMG criteria used for classification: PVS1_Very Strong, PM2. -

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: chr20-16293000;