5-132703607-A-C

Position:

• chr5-132703607-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001300791.2(KIF3A):​c.1322T>G​(p.Val441Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: KIF3A NM_001300791.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.23

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]

ENSG00000230612 (HGNC:):

ACMG classification

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=0.19212309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3A	NM_001300791.2	c.1322T>G	p.Val441Gly	missense_variant	12/19	ENST00000403231.6	NP_001287720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3A	ENST00000403231.6	c.1322T>G	p.Val441Gly	missense_variant	12/19	2	NM_001300791.2	ENSP00000385808.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1241T>G (p.V414G) alteration is located in exon 10 (coding exon 10) of the KIF3A gene. This alteration results from a T to G substitution at nucleotide position 1241, causing the valine (V) at amino acid position 414 to be replaced by a glycine (G). 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	0.44
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	25
DANN	Benign	0.86
DEOGEN2	Uncertain	0.66	D;T;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.073
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.56	T;T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.8	L;.;.;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.2	D;D;.;D
REVEL	Benign	0.14
Sift	Benign	0.22	T;T;.;D
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0	B;.;.;B
Vest4		0.33
MutPred		0.25		.;.;.;Gain of relative solvent accessibility (P = 0.005);
MVP		0.46
MPC		0.90
ClinPred		0.81	D
GERP RS		5.4
Varity_R		0.26
gMVP		0.52

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: chr5-132039299;