chr6-33404089-A-C

Variant names:

• chr6-33404089-A-C
• NM_002263.4:c.716A>C

Variant summary

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

The NM_002263.4(KIFC1):​c.716A>C​(p.Glu239Ala) 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. 16/21 in silico tools predict 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: 1.51

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=0.13447475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.716A>C	p.Glu239Ala	missense_variant	Exon 6 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.716A>C	p.Glu239Ala	missense_variant	Exon 6 of 12		XP_011512887.1
KIFC1	XM_017010837.2	c.593A>C	p.Glu198Ala	missense_variant	Exon 6 of 11		XP_016866326.2
KIFC1	XM_011514587.3	c.716A>C	p.Glu239Ala	missense_variant	Exon 6 of 10		XP_011512889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC1	ENST00000428849.7	c.716A>C	p.Glu239Ala	missense_variant	Exon 6 of 11	1	NM_002263.4	ENSP00000393963.2
KIFC1	ENST00000450504.1	c.*230A>C		downstream_gene_variant		3		ENSP00000409539.1
KIFC1	ENST00000486695.1	n.*223A>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Benign	0.83
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.81	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.3	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.17
Sift	Benign	0.31	T
Sift4G	Benign	0.68	T
Polyphen		0.0020	B
Vest4		0.23
MutPred		0.37		Gain of MoRF binding (P = 0.0134);
MVP		0.86
MPC		0.42
ClinPred		0.092	T
GERP RS		2.6
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.1
Varity_R		0.088
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr6-33371866;