6-168033900-G-A

Position:

• chr6-168033900-G-A

Variant summary

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

The NM_030615.4(KIF25):​c.186G>A​(p.Met62Ile) variant causes a missense change. 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: KIF25 NM_030615.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.23

Genes affected

KIF25 (HGNC:6390): (kinesin family member 25) The protein encoded by this gene is a member of the kinesin-like protein family. Protein family members are microtubule-dependent molecular motors that transport organelles within cells and move chromosomes during cell division. However, the particular function of this gene product has not yet been determined. Two alternatively spliced transcript variants which encode products have been described. Other splice variants have been found that lack exon 2 and the initiation codon for translation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF25	NM_030615.4	c.186G>A	p.Met62Ile	missense_variant	8/13	ENST00000643607.3	NP_085118.2
KIF25	NM_005355.5	c.186G>A	p.Met62Ile	missense_variant	8/12		NP_005346.3
KIF25	XM_047418749.1	c.186G>A	p.Met62Ile	missense_variant	6/11		XP_047274705.1
KIF25	XM_011535803.4	c.186G>A	p.Met62Ile	missense_variant	6/10		XP_011534105.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF25	ENST00000643607.3	c.186G>A	p.Met62Ile	missense_variant	8/13		NM_030615.4	ENSP00000496229.1

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

Apr 06, 2023

The c.186G>A (p.M62I) alteration is located in exon 4 (coding exon 3) of the KIF25 gene. This alteration results from a G to A substitution at nucleotide position 186, causing the methionine (M) at amino acid position 62 to be replaced by an isoleucine (I). 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	0.39
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T;T;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.96	.;.;D;D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.28	T
MutationAssessor	Benign	0.94	L;L;L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-3.0	.;D;D;D
REVEL	Uncertain	0.52
Sift	Benign	0.040	.;D;D;D
Sift4G	Benign	0.15	.;T;T;T
Polyphen		0.64	P;P;P;D
Vest4		0.60, 0.59
MutPred		0.67		Loss of catalytic residue at M62 (P = 0.0409);Loss of catalytic residue at M62 (P = 0.0409);Loss of catalytic residue at M62 (P = 0.0409);Loss of catalytic residue at M62 (P = 0.0409);
MVP		0.71
MPC		0.51
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.74
gMVP		0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 2
DS_AL_spliceai		0.32		Position offset: -18

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: chr6-168434580;