NM_030615.4:c.113C>T

Variant names:

• chr6-168030793-C-T
• rs146495006
• NM_030615.4:c.113C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_030615.4(KIF25):​c.113C>T​(p.Ser38Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000713 in 1,613,206 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: KIF25 NM_030615.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.38835248).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030615.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF25	NM_030615.4	MANE Select	c.113C>T	p.Ser38Phe	missense	Exon 7 of 13	NP_085118.2	Q9UIL4-1
	KIF25	NM_005355.5		c.113C>T	p.Ser38Phe	missense	Exon 7 of 12	NP_005346.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF25	ENST00000643607.3	MANE Select	c.113C>T	p.Ser38Phe	missense	Exon 7 of 13	ENSP00000496229.1	Q9UIL4-1
	KIF25	ENST00000443060.6	TSL:5	c.113C>T	p.Ser38Phe	missense	Exon 4 of 10	ENSP00000388878.2	Q9UIL4-1
	KIF25	ENST00000955753.1		c.113C>T	p.Ser38Phe	missense	Exon 5 of 10	ENSP00000625812.1

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152120 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.000103

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000599 AC: 15 AN: 250430 AF XY: 0.0000517

Gnomad AFR exome AF: 0.0000617

Gnomad AMR exome AF: 0.000117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000650 AC: 95 AN: 1460968 Hom.: 0 Cov.: 30 AF XY: 0.0000592 AC XY: 43 AN XY: 726842

African (AFR) AF: 0.000299 AC: 10 AN: 33410

American (AMR) AF: 0.000112 AC: 5 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39612

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86078

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5766

European-Non Finnish (NFE) AF: 0.0000450 AC: 50 AN: 1111646

Other (OTH) AF: 0.000381 AC: 23 AN: 60366

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152238 Hom.: 1 Cov.: 32 AF XY: 0.0000940 AC XY: 7 AN XY: 74442

African (AFR) AF: 0.000217 AC: 9 AN: 41534

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68038

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.000159

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.000437

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Benign	-0.040
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.18
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.51
MVP		0.72
MPC		0.51
ClinPred		0.61	D
GERP RS		3.4
Varity_R		0.74
gMVP		0.73
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs146495006; hg19: chr6-168431473;