chr6-33403774-G-C

Variant names:

• chr6-33403774-G-C
• rs767111043
• NM_002263.4:c.401G>C

Variant summary

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

The NM_002263.4(KIFC1):​c.401G>C​(p.Arg134Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 6.16

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.401G>C	p.Arg134Pro	missense_variant	Exon 6 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.401G>C	p.Arg134Pro	missense_variant	Exon 6 of 12		XP_011512887.1
KIFC1	XM_017010837.2	c.278G>C	p.Arg93Pro	missense_variant	Exon 6 of 11		XP_016866326.2
KIFC1	XM_011514587.3	c.401G>C	p.Arg134Pro	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.401G>C	p.Arg134Pro	missense_variant	Exon 6 of 11	1	NM_002263.4	ENSP00000393963.2
KIFC1	ENST00000450504.1	c.524G>C	p.Arg175Pro	missense_variant	Exon 7 of 7	3		ENSP00000409539.1
KIFC1	ENST00000486695.1	n.575G>C		non_coding_transcript_exon_variant	Exon 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251210 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135784

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461746 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727166

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.67
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	.;D
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.73	D;D
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.49
MutPred		0.37		Loss of MoRF binding (P = 5e-04);.;
MVP		0.93
MPC		1.5
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.68
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs767111043; hg19: chr6-33371551;