chr5-132702138-C-A

Variant summary

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

The NM_001300791.2(KIF3A):​c.1833G>T​(p.Glu611Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

KIF3A
NM_001300791.2 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.930
Variant links:
Genes affected
KIF3A (HGNC:6319): (kinesin family member 3A) Enables protein phosphatase binding activity; small GTPase binding activity; and spectrin binding activity. Involved in protein localization to cell junction and protein transport. Located in centriole and centrosome. Part of kinesin II complex. Colocalizes with spindle 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 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF3ANM_001300791.2 linkuse as main transcriptc.1833G>T p.Glu611Asp missense_variant 15/19 ENST00000403231.6 NP_001287720.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF3AENST00000403231.6 linkuse as main transcriptc.1833G>T p.Glu611Asp missense_variant 15/192 NM_001300791.2 ENSP00000385808
ENST00000628061.1 linkuse as main transcriptn.111+12304C>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251422
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461636
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727122
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsMay 08, 2024The c.1752G>T (p.E584D) alteration is located in exon 13 (coding exon 13) of the KIF3A gene. This alteration results from a G to T substitution at nucleotide position 1752, causing the glutamic acid (E) at amino acid position 584 to be replaced by an aspartic acid (D). 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
0.27
BayesDel_addAF
Benign
-0.20
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T;T;T;.
Eigen
Benign
0.012
Eigen_PC
Benign
-0.026
FATHMM_MKL
Benign
0.43
N
LIST_S2
Uncertain
0.91
D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.52
D;D;D;D
MetaSVM
Benign
-1.2
T
MutationAssessor
Uncertain
2.3
M;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-2.1
N;N;.;N
REVEL
Benign
0.17
Sift
Benign
0.055
T;T;.;T
Sift4G
Benign
0.080
T;T;T;T
Polyphen
0.0060
B;.;.;P
Vest4
0.75
MutPred
0.20
.;.;.;Gain of MoRF binding (P = 0.1157);
MVP
0.34
MPC
0.63
ClinPred
0.58
D
GERP RS
2.9
Varity_R
0.29
gMVP
0.72

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: rs1441407508; hg19: chr5-132037830; API