2-25929464-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002254.8(KIF3C):ā€‹c.2129T>Cā€‹(p.Met710Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000018 ( 0 hom. )

Consequence

KIF3C
NM_002254.8 missense

Scores

2
9
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.17
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF3CNM_002254.8 linkuse as main transcriptc.2129T>C p.Met710Thr missense_variant 7/8 ENST00000264712.8 NP_002245.4
KIF3CXM_005264299.4 linkuse as main transcriptc.2126T>C p.Met709Thr missense_variant 7/8 XP_005264356.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF3CENST00000264712.8 linkuse as main transcriptc.2129T>C p.Met710Thr missense_variant 7/81 NM_002254.8 ENSP00000264712 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152140
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
250872
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135626
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461752
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727168
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.0000243
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152140
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000606
Hom.:
0
Bravo
AF:
0.0000113
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsJun 28, 2023The c.2129T>C (p.M710T) alteration is located in exon 7 (coding exon 7) of the KIF3C gene. This alteration results from a T to C substitution at nucleotide position 2129, causing the methionine (M) at amino acid position 710 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
Pathogenic
0.68
BayesDel_addAF
Benign
-0.038
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
23
DANN
Uncertain
0.98
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.29
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.72
.;T
M_CAP
Uncertain
0.098
D
MetaRNN
Uncertain
0.63
D;D
MetaSVM
Benign
-0.48
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Uncertain
0.49
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0060
D;D
Vest4
0.66
MVP
0.42
MPC
0.65
ClinPred
0.40
T
GERP RS
5.6
gMVP
0.76

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.

Other links and lift over

dbSNP: rs367912211; hg19: chr2-26152333; API