NM_001369769.2:c.11T>C

Variant names:

• chr8-144466430-T-C
• NM_001369769.2:c.11T>C

Variant summary

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

The NM_001369769.2(KIFC2):​c.11T>C​(p.Phe4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000843 in 1,185,566 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: 30)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.57

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 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
KIFC2	NM_001369769.2	c.11T>C	p.Phe4Ser	missense_variant	Exon 1 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.11T>C	p.Phe4Ser	missense_variant	Exon 1 of 18		NM_001369769.2	ENSP00000494595.1
KIFC2	ENST00000301332.3	c.11T>C	p.Phe4Ser	missense_variant	Exon 1 of 17	1		ENSP00000301332.2
KIFC2	ENST00000642354.1	c.11T>C	p.Phe4Ser	missense_variant	Exon 1 of 18			ENSP00000496539.1
KIFC2	ENST00000643461.1	n.388T>C		non_coding_transcript_exon_variant	Exon 1 of 17

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.43e-7 AC: 1 AN: 1185566 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 587310

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: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	.;.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.093
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Pathogenic	0.95	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Benign	1.7	.;.;L
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.96	.;.;N
REVEL	Uncertain	0.55
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		0.98	.;.;D
Vest4		0.57
MutPred		0.34		Gain of disorder (P = 3e-04);Gain of disorder (P = 3e-04);Gain of disorder (P = 3e-04);
MVP		0.89
ClinPred		0.87	D
GERP RS		3.8
Varity_R		0.31
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: chr8-145691813;