6-33403497-A-C

Variant names:

• chr6-33403497-A-C
• NM_002263.4:c.317A>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.317A>C​(p.Gln106Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KIFC1 NM_002263.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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=0.20397866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.317A>C	p.Gln106Pro	missense_variant	Exon 5 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.317A>C	p.Gln106Pro	missense_variant	Exon 5 of 12		XP_011512887.1
KIFC1	XM_017010837.2	c.194A>C	p.Gln65Pro	missense_variant	Exon 5 of 11		XP_016866326.2
KIFC1	XM_011514587.3	c.317A>C	p.Gln106Pro	missense_variant	Exon 5 of 10		XP_011512889.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC1	ENST00000428849.7	c.317A>C	p.Gln106Pro	missense_variant	Exon 5 of 11	1	NM_002263.4	ENSP00000393963.2
KIFC1	ENST00000450504.1	c.440A>C	p.Gln147Pro	missense_variant	Exon 6 of 7	3		ENSP00000409539.1
KIFC1	ENST00000486695.1	n.491A>C		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727238

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.3	M;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.76	N;D
REVEL	Benign	0.28
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.27	T;D
Polyphen		0.84	P;.
Vest4		0.29
MutPred		0.22		Gain of glycosylation at Q106 (P = 0.0439);.;
MVP		0.78
MPC		0.47
ClinPred		0.43	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-33371274;