6-33404961-G-T

Variant names:

• chr6-33404961-G-T
• rs147773024
• NM_002263.4:c.866G>T

Variant summary

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

The NM_002263.4(KIFC1):​c.866G>T​(p.Arg289Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIFC1 NM_002263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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=0.2362856).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.866G>T	p.Arg289Leu	missense_variant	Exon 7 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.866G>T	p.Arg289Leu	missense_variant	Exon 7 of 12		XP_011512887.1
KIFC1	XM_017010837.2	c.743G>T	p.Arg248Leu	missense_variant	Exon 7 of 11		XP_016866326.2
KIFC1	XM_011514587.3	c.756+832G>T		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.866G>T	p.Arg289Leu	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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.072	T
Eigen	Benign	0.17
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.013	D
Sift4G	Benign	0.13	T
Polyphen		0.85	P
Vest4		0.38
MutPred		0.45		Loss of MoRF binding (P = 0.0707);
MVP		0.91
MPC		0.94
ClinPred		0.94	D
GERP RS		4.2
Varity_R		0.16
gMVP		0.62

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

LitVar

Other links and lift over

dbSNP: rs147773024; hg19: chr6-33372738;