8-144467094-C-G

Variant names:

• chr8-144467094-C-G
• NM_001369769.2:c.314C>G

Variant summary

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

The NM_001369769.2(KIFC2):​c.314C>G​(p.Pro105Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P105S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 35)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.954

Genes affected

KIFC2 (HGNC:29530): (kinesin family member C2) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement and mitotic spindle assembly. Predicted to be located in cytoplasm. Predicted to be part of kinesin complex. Predicted to be active in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TMEM276 (HGNC:56235): (transmembrane protein 276)

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=0.15670764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.314C>G	p.Pro105Arg	missense_variant	Exon 3 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.314C>G	p.Pro105Arg	missense_variant	Exon 3 of 18		NM_001369769.2	ENSP00000494595.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446882 Hom.: 0 Cov.: 65 AF XY: 0.00000139 AC XY: 1 AN XY: 718654

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: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0051	.;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.51	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	.;.;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.20	.;.;N
REVEL	Benign	0.091
Sift	Uncertain	0.0010	.;.;D
Sift4G	Uncertain	0.0030	.;.;D
Polyphen		0.87	.;.;P
Vest4		0.44
MutPred		0.14		Loss of glycosylation at S101 (P = 0.098);Loss of glycosylation at S101 (P = 0.098);Loss of glycosylation at S101 (P = 0.098);
MVP		0.67
ClinPred		0.78	D
GERP RS		4.2
Varity_R		0.078
gMVP		0.19

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-145692477;