6-168033981-C-A

Variant names:

• chr6-168033981-C-A
• rs150299707
• NM_030615.4:c.267C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_030615.4(KIF25):​c.267C>A​(p.Asp89Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,614,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: KIF25 NM_030615.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.272
• Publications: 3 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.017964095).
• BP6: Variant 6-168033981-C-A is Benign according to our data. Variant chr6-168033981-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3288551.Status of the report is criteria_provided_single_submitter, 1 stars.

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.267C>A	p.Asp89Glu	missense	Exon 8 of 13	NP_085118.2	Q9UIL4-1
	KIF25	NM_005355.5		c.267C>A	p.Asp89Glu	missense	Exon 8 of 12	NP_005346.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF25	ENST00000643607.3	MANE Select	c.267C>A	p.Asp89Glu	missense	Exon 8 of 13	ENSP00000496229.1	Q9UIL4-1
	KIF25	ENST00000443060.6	TSL:5	c.267C>A	p.Asp89Glu	missense	Exon 5 of 10	ENSP00000388878.2	Q9UIL4-1
	KIF25	ENST00000955753.1		c.267C>A	p.Asp89Glu	missense	Exon 6 of 10	ENSP00000625812.1

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152174 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000705

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000398 AC: 100 AN: 251442 AF XY: 0.000331

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000756

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.000287 AC: 420 AN: 1461880 Hom.: 0 Cov.: 31 AF XY: 0.000275 AC XY: 200 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000331 AC: 368 AN: 1112000

Other (OTH) AF: 0.000331 AC: 20 AN: 60396

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152174 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74346

African (AFR) AF: 0.0000724 AC: 3 AN: 41438

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

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

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000705 AC: 48 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000469 Hom.: 0

Bravo AF: 0.000280

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000511 AC: 62

EpiCase AF: 0.000600

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.12
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.0040
DANN	Benign	0.27
DEOGEN2	Benign	0.047	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.045	N
PhyloP100		-0.27
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.087
Sift	Benign	0.82	T
Sift4G	Benign	1.0	T
Polyphen		0.0080	B
Vest4		0.10
MutPred		0.38		Gain of catalytic residue at D89 (P = 0.037)
MVP		0.24
MPC		0.096
ClinPred		0.025	T
GERP RS		-8.4
Varity_R		0.022
gMVP		0.11
Mutation Taster		=99/1	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: rs150299707; hg19: chr6-168434661;