6-33403497-A-G

Variant names:

• chr6-33403497-A-G
• rs1775480812
• NM_002263.4:c.317A>G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002263.4(KIFC1):​c.317A>G​(p.Gln106Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000752 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: KIFC1 NM_002263.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.093057305).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC1	NM_002263.4	c.317A>G	p.Gln106Arg	missense_variant	Exon 5 of 11	ENST00000428849.7	NP_002254.2
KIFC1	XM_011514585.2	c.317A>G	p.Gln106Arg	missense_variant	Exon 5 of 12		XP_011512887.1
KIFC1	XM_017010837.2	c.194A>G	p.Gln65Arg	missense_variant	Exon 5 of 11		XP_016866326.2
KIFC1	XM_011514587.3	c.317A>G	p.Gln106Arg	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>G	p.Gln106Arg	missense_variant	Exon 5 of 11	1	NM_002263.4	ENSP00000393963.2
KIFC1	ENST00000450504.1	c.440A>G	p.Gln147Arg	missense_variant	Exon 6 of 7	3		ENSP00000409539.1
KIFC1	ENST00000486695.1	n.491A>G		non_coding_transcript_exon_variant	Exon 3 of 4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000752 AC: 11 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 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: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.317A>G (p.Q106R) alteration is located in exon 5 (coding exon 5) of the KIFC1 gene. This alteration results from a A to G substitution at nucleotide position 317, causing the glutamine (Q) at amino acid position 106 to be replaced by an arginine (R). 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	0.079
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.062
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.59	.;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.093	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.13	N;D
REVEL	Benign	0.086
Sift	Benign	0.35	T;D
Sift4G	Benign	0.53	T;D
Polyphen		0.0030	B;.
Vest4		0.096
MutPred		0.22		Gain of MoRF binding (P = 0.0245);.;
MVP		0.70
MPC		0.42
ClinPred		0.12	T
GERP RS		4.1
Varity_R		0.070
gMVP		0.41

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: rs1775480812; hg19: chr6-33371274;