Variant 2-25929027-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_002254.8(KIF3C):c.2333C>G(p.Ser778Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000175 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

KIF3C
NM_002254.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10075495).

BS2

High AC in GnomAd4 at 35 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3C	NM_002254.8 linkuse as main transcript	c.2333C>G	p.Ser778Cys	missense_variant	8/8	ENST00000264712.8	NP_002245.4
KIF3C	XM_005264299.4 linkuse as main transcript	c.2330C>G	p.Ser777Cys	missense_variant	8/8		XP_005264356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KIF3C	ENST00000264712.8 linkuse as main transcript	c.2333C>G	p.Ser778Cys	missense_variant	8/8	1	NM_002254.8	ENSP00000264712	P1
KIF3C	ENST00000417737.5 linkuse as main transcript	c.*389C>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	1		ENSP00000393676
KIF3C	ENST00000455394.5 linkuse as main transcript	c.*438C>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	1		ENSP00000410407
KIF3C	ENST00000405914.1 linkuse as main transcript	c.2333C>G	p.Ser778Cys	missense_variant	9/9	5		ENSP00000385030	P1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000159

AC:

AN:

251014

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000247

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000170

AC:

248

AN:

1461610

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

126

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000421

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000135

Gnomad4 OTH exome

AF:

0.000431

GnomAD4 genome

AF:

0.000230

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000213

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000593

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

Jan 24, 2023

The c.2333C>G (p.S778C) alteration is located in exon 8 (coding exon 8) of the KIF3C gene. This alteration results from a C to G substitution at nucleotide position 2333, causing the serine (S) at amino acid position 778 to be replaced by a cysteine (C). 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

0.085

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

0.085

Eigen_PC

Benign

0.21

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

.;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.72

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.6

D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0090

D;D

Sift4G

Uncertain

0.031

D;D

Vest4

0.30

MVP

0.43

MPC

0.57

ClinPred

0.068

GERP RS

4.7

gMVP

0.63

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over