2-25955645-T-A

Position:

• chr2-25955645-T-A

Variant summary

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

The NM_002254.8(KIF3C):​c.1666A>T​(p.Met556Leu) 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. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF3C NM_002254.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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 (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=0.1789394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF3C	NM_002254.8	c.1666A>T	p.Met556Leu	missense_variant	3/8	ENST00000264712.8	NP_002245.4
KIF3C	XM_005264299.4	c.1666A>T	p.Met556Leu	missense_variant	3/8		XP_005264356.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF3C	ENST00000264712.8	c.1666A>T	p.Met556Leu	missense_variant	3/8	1	NM_002254.8	ENSP00000264712.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 13, 2022

The c.1666A>T (p.M556L) alteration is located in exon 3 (coding exon 3) of the KIF3C gene. This alteration results from a A to T substitution at nucleotide position 1666, causing the methionine (M) at amino acid position 556 to be replaced by a leucine (L). 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	0.18
BayesDel_addAF	Benign	0.00070	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	23
DANN	Benign	0.74
Eigen	Benign	-0.14
Eigen_PC	Benign	0.068
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.87	T
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.23
Sift	Benign	0.71	T;T
Sift4G	Benign	0.70	T;T
Vest4		0.34
MutPred		0.47		Loss of MoRF binding (P = 0.0922);Loss of MoRF binding (P = 0.0922);
MVP		0.38
MPC		0.52
ClinPred		0.93	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.34

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: chr2-26178514; COSMIC: COSV53101992; COSMIC: COSV53101992;