2-148875696-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004522.3(KIF5C):​c.79G>A​(p.Asp27Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

KIF5C
NM_004522.3 missense

Scores

4
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.62
Variant links:
Genes affected
KIF5C (HGNC:6325): (kinesin family member 5C) The protein encoded by this gene is a kinesin heavy chain subunit involved in the transport of cargo within the central nervous system. The encoded protein, which acts as a tetramer by associating with another heavy chain and two light chains, interacts with protein kinase CK2. Mutations in this gene have been associated with complex cortical dysplasia with other brain malformations-2. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene. [provided by RefSeq, Jul 2015]
KIF5C-AS1 (HGNC:40325): (KIF5C antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), KIF5C. . Gene score misZ 4.0539 (greater than the threshold 3.09). Trascript score misZ 3.6179 (greater than threshold 3.09). GenCC has associacion of gene with complex cortical dysplasia with other brain malformations 2.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF5CNM_004522.3 linkuse as main transcriptc.79G>A p.Asp27Asn missense_variant 1/26 ENST00000435030.6 NP_004513.1
KIF5C-AS1XR_001739733.2 linkuse as main transcriptn.7622C>T non_coding_transcript_exon_variant 4/4
KIF5CXM_017004062.2 linkuse as main transcriptc.79G>A p.Asp27Asn missense_variant 1/26 XP_016859551.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF5CENST00000435030.6 linkuse as main transcriptc.79G>A p.Asp27Asn missense_variant 1/261 NM_004522.3 ENSP00000393379 P4O60282-1
KIF5C-AS1ENST00000601658.5 linkuse as main transcriptn.676+1530C>T intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 04, 2024The c.79G>A (p.D27N) alteration is located in exon 1 (coding exon 1) of the KIF5C gene. This alteration results from a G to A substitution at nucleotide position 79, causing the aspartic acid (D) at amino acid position 27 to be replaced by an asparagine (N). 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
0.79
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.27
T
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D
M_CAP
Pathogenic
0.72
D
MetaRNN
Uncertain
0.50
D
MetaSVM
Benign
-0.78
T
MutationTaster
Benign
1.0
D
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.25
Sift
Benign
0.17
T
Sift4G
Benign
0.10
T
Polyphen
0.14
B
Vest4
0.46
MutPred
0.47
Gain of methylation at K28 (P = 0.0684);
MVP
0.65
MPC
1.6
ClinPred
0.95
D
GERP RS
4.1
Varity_R
0.18
gMVP
0.82

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.

Other links and lift over

hg19: chr2-149633265; API