Variant 2-25956404-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000264712.8(KIF3C):c.1586T>C(p.Met529Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KIF3C
ENST00000264712.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.37

Variant links:

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 links:

KIF3C (HGNC:):

KIF3C links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20090276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3C	NM_002254.8 linkuse as main transcript	c.1586T>C	p.Met529Thr	missense_variant	2/8	ENST00000264712.8	NP_002245.4	O14782A2RU78
KIF3C	XM_005264299.4 linkuse as main transcript	c.1586T>C	p.Met529Thr	missense_variant	2/8		XP_005264356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3C	ENST00000264712.8 linkuse as main transcript	c.1586T>C	p.Met529Thr	missense_variant	2/8	1	NM_002254.8	ENSP00000264712.3		O14782

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.1586T>C (p.M529T) alteration is located in exon 2 (coding exon 2) of the KIF3C gene. This alteration results from a T to C substitution at nucleotide position 1586, causing the methionine (M) at amino acid position 529 to be replaced by a threonine (T). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Benign

-0.057

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.037

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.16

Sift

Benign

0.050

D;D

Sift4G

Benign

0.19

T;T

Vest4

0.34

MutPred

0.34

Loss of stability (P = 0.0078);Loss of stability (P = 0.0078);

MVP

0.22

MPC

0.65

ClinPred

0.68

GERP RS

5.4

gMVP

0.53

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over