6-33405191-C-A

Variant names:

• chr6-33405191-C-A
• rs371098598
• NM_002263.4:c.1096C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002263.4(KIFC1):​c.1096C>A​(p.Pro366Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIFC1 NM_002263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.899

Genes affected

KIFC1 (HGNC:6389): (kinesin family member C1) Predicted to enable microtubule binding activity and minus-end-directed microtubule motor activity. Involved in mitotic metaphase plate congression and mitotic spindle assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073453754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.1096C>A	p.Pro366Thr	missense_variant	Exon 7 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.1096C>A	p.Pro366Thr	missense_variant	Exon 7 of 12		XP_011512887.1
KIFC1	XM_017010837.2	c.973C>A	p.Pro325Thr	missense_variant	Exon 7 of 11		XP_016866326.2
KIFC1	XM_011514587.3	c.757-1005C>A		intron_variant	Intron 6 of 9		XP_011512889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC1	ENST00000428849.7	c.1096C>A	p.Pro366Thr	missense_variant	Exon 7 of 11	1	NM_002263.4	ENSP00000393963.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1096C>A (p.P366T) alteration is located in exon 7 (coding exon 7) of the KIFC1 gene. This alteration results from a C to A substitution at nucleotide position 1096, causing the proline (P) at amino acid position 366 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.67
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.34	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.60	N
PrimateAI	Uncertain	0.48	T
PROVEAN	Benign	0.84	N
REVEL	Benign	0.055
Sift	Benign	0.57	T
Sift4G	Benign	0.64	T
Polyphen		0.0030	B
Vest4		0.25
MutPred		0.43		Gain of phosphorylation at P366 (P = 0.0089);
MVP		0.33
MPC		0.45
ClinPred		0.060	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.9
Varity_R		0.066
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs371098598; hg19: chr6-33372968;