16-57760832-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001130100.2(KIFC3):​c.2126C>G​(p.Ala709Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000559 in 1,613,286 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00059 (1 hom.)
• Consequence: KIFC3 NM_001130100.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21672499).
• BS2: High AC in GnomAd4 at 44 AD gene.

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>G	p.Ala709Gly	missense	Exon 16 of 20	NP_001123572.1	Q9BVG8-2
	KIFC3	NM_001318710.2		c.2192C>G	p.Ala731Gly	missense	Exon 16 of 20	NP_001305639.1	Q9BVG8-6
	KIFC3	NM_005550.4		c.2126C>G	p.Ala709Gly	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>G	p.Ala709Gly	missense	Exon 16 of 20	ENSP00000401696.2	Q9BVG8-2
	KIFC3	ENST00000379655.8	TSL:1	c.2126C>G	p.Ala709Gly	missense	Exon 16 of 19	ENSP00000368976.4	Q9BVG8-3
	KIFC3	ENST00000465878.6	TSL:1	c.1709C>G	p.Ala570Gly	missense	Exon 16 of 20	ENSP00000454659.1	Q9BVG8-5

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000276 AC: 69 AN: 250000 AF XY: 0.000258

Gnomad AFR exome AF: 0.0000618

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000468

Gnomad NFE exome AF: 0.000584

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000587 AC: 858 AN: 1461070 Hom.: 1 Cov.: 32 AF XY: 0.000563 AC XY: 409 AN XY: 726872

African (AFR) AF: 0.000119 AC: 4 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: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52644

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

European-Non Finnish (NFE) AF: 0.000746 AC: 830 AN: 1111982

Other (OTH) AF: 0.000348 AC: 21 AN: 60390

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18 AN XY: 74368

African (AFR) AF: 0.000121 AC: 5 AN: 41456

American (AMR) AF: 0.000131 AC: 2 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000404 Hom.: 0

Bravo AF: 0.000295

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000382

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.067
Eigen_PC	Benign	0.079
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.9	L
PhyloP100		4.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.23
Sift	Benign	0.62	T
Sift4G	Benign	0.59	T
Polyphen		0.033	B
Vest4		0.32
MVP		0.70
MPC		0.59
ClinPred		0.072	T
GERP RS		5.0
PromoterAI		-0.0034	Neutral
Varity_R		0.24
gMVP		0.10
Mutation Taster		=75/25	polymorphism

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

Other links and lift over

dbSNP: rs147963864; hg19: chr16-57794744; COSMIC: COSV65553528; COSMIC: COSV65553528;