chr16-57760832-G-A

Variant names:

• chr16-57760832-G-A
• rs147963864
• NM_001130100.2:c.2126C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001130100.2(KIFC3):​c.2126C>T​(p.Ala709Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. A709G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: KIFC3 NM_001130100.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.08
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41670635).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130100.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC3	NM_001130100.2	MANE Select	c.2126C>T	p.Ala709Val	missense	Exon 16 of 20	NP_001123572.1	Q9BVG8-2
	KIFC3	NM_001318710.2		c.2192C>T	p.Ala731Val	missense	Exon 16 of 20	NP_001305639.1	Q9BVG8-6
	KIFC3	NM_005550.4		c.2126C>T	p.Ala709Val	missense	Exon 16 of 19	NP_005541.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC3	ENST00000445690.7	TSL:1 MANE Select	c.2126C>T	p.Ala709Val	missense	Exon 16 of 20	ENSP00000401696.2	Q9BVG8-2
	KIFC3	ENST00000379655.8	TSL:1	c.2126C>T	p.Ala709Val	missense	Exon 16 of 19	ENSP00000368976.4	Q9BVG8-3
	KIFC3	ENST00000465878.6	TSL:1	c.1709C>T	p.Ala570Val	missense	Exon 16 of 20	ENSP00000454659.1	Q9BVG8-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250000 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461070 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726872

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52644

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111982

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.0049
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.1
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.27
Sift	Benign	0.16	T
Sift4G	Benign	0.52	T
Polyphen		0.70	P
Vest4		0.37
MutPred		0.66		Gain of MoRF binding (P = 0.1209)
MVP		0.70
MPC		0.70
ClinPred		0.43	T
GERP RS		5.0
PromoterAI		0.0015	Neutral
Varity_R		0.22
gMVP		0.14
Mutation Taster		=81/19	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs147963864; hg19: chr16-57794744; COSMIC: COSV65551524; COSMIC: COSV65551524;