16-57765550-T-G

Position:

• chr16-57765550-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001130100.2(KIFC3):​c.1421A>C​(p.Asp474Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000413 in 1,452,196 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: KIFC3 NM_001130100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

Genes affected

KIFC3 (HGNC:6326): (kinesin family member C3) This gene encodes a member of the kinesin-14 family of microtubule motors. Members of this family play a role in the formation, maintenance and remodeling of the bipolar mitotic spindle. The protein encoded by this gene has cytoplasmic functions in the interphase cells. It may also be involved in the final stages of cytokinesis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

KIFC3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFC3	NM_001130100.2	c.1421A>C	p.Asp474Ala	missense_variant	11/20	ENST00000445690.7	NP_001123572.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFC3	ENST00000445690.7	c.1421A>C	p.Asp474Ala	missense_variant	11/20	1	NM_001130100.2	ENSP00000401696.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000413 AC: 6 AN: 1452196 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721366

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: 0.0000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000452

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2023

The c.1421A>C (p.D474A) alteration is located in exon 11 (coding exon 10) of the KIFC3 gene. This alteration results from a A to C substitution at nucleotide position 1421, causing the aspartic acid (D) at amino acid position 474 to be replaced by an alanine (A). 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	0.11
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	.;T;.;.;.;.;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.071
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	.;D;D;.;D;D;D;D
M_CAP	Benign	0.069	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	1.4	.;L;L;.;.;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D;D;D
REVEL	Uncertain	0.48
Sift	Benign	0.030	D;T;T;D;T;D;D;D
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T
Polyphen		0.96, 0.083, 0.36	.;D;.;.;.;B;B;.
Vest4		0.47
MVP		0.83
MPC		1.4
ClinPred		0.92	D
GERP RS		5.4
Varity_R		0.38
gMVP		0.66

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

LitVar

Other links and lift over

dbSNP: rs2050393107; hg19: chr16-57799462;