2-25954268-T-G

Position:

• chr2-25954268-T-G

Variant summary

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

The ENST00000264712.8(KIF3C):​c.1888A>C​(p.Lys630Gln) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.00093 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KIF3C ENST00000264712.8 missense, splice_region
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.89

Genes affected

KIF3C (HGNC:6321): (kinesin family member 3C) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement. Predicted to act upstream of or within organelle transport along microtubule. Predicted to be located in microtubule cytoskeleton; neuronal cell body; and neuronal ribonucleoprotein granule. Predicted to be part of kinesin complex. Predicted to be active in microtubule. [provided by Alliance of Genome Resources, Apr 2022]

KIF3C (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3C	NM_002254.8	c.1888A>C	p.Lys630Gln	missense_variant, splice_region_variant	4/8	ENST00000264712.8	NP_002245.4
KIF3C	XM_005264299.4	c.1888A>C	p.Lys630Gln	missense_variant, splice_region_variant	4/8		XP_005264356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3C	ENST00000264712.8	c.1888A>C	p.Lys630Gln	missense_variant, splice_region_variant	4/8	1	NM_002254.8	ENSP00000264712.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000931 AC: 1354 AN: 1454110 Hom.: 0 Cov.: 29 AF XY: 0.000806 AC XY: 583 AN XY: 723658

Gnomad4 AFR exome AF: 0.000750

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.000267

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.000732

GnomAD4 genome Cov.: 31

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

Jan 25, 2023

The c.1888A>C (p.K630Q) alteration is located in exon 4 (coding exon 4) of the KIF3C gene. This alteration results from a A to C substitution at nucleotide position 1888, causing the lysine (K) at amino acid position 630 to be replaced by a glutamine (Q). 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	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	29
DANN	Benign	0.93
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.083	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.63	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.44
Sift	Benign	0.41	T;T
Sift4G	Benign	0.19	T;T
Vest4		0.59
MutPred		0.33		Loss of ubiquitination at K630 (P = 0.0107);Loss of ubiquitination at K630 (P = 0.0107);
MVP		0.62
MPC		0.60
ClinPred		0.82	D
GERP RS		4.8
gMVP		0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.070		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: chr2-26177137;