rs780114962

Variant names:

• chr6-168033974-C-G
• rs780114962
• NM_030615.4:c.260C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-168033974-C-G
• chr6-168033974-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030615.4(KIF25):​c.260C>G​(p.Pro87Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P87L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KIF25 NM_030615.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22761723).

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.260C>G	p.Pro87Arg	missense	Exon 8 of 13	NP_085118.2	Q9UIL4-1
	KIF25	NM_005355.5		c.260C>G	p.Pro87Arg	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.260C>G	p.Pro87Arg	missense	Exon 8 of 13	ENSP00000496229.1	Q9UIL4-1
	KIF25	ENST00000443060.6	TSL:5	c.260C>G	p.Pro87Arg	missense	Exon 5 of 10	ENSP00000388878.2	Q9UIL4-1
	KIF25	ENST00000955753.1		c.260C>G	p.Pro87Arg	missense	Exon 6 of 10	ENSP00000625812.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251456 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

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

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	1.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.047
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.18
Sift	Benign	0.059	T
Sift4G	Benign	0.073	T
Polyphen		0.97	D
Vest4		0.20
MutPred		0.46		Loss of disorder (P = 0.1224)
MVP		0.59
MPC		0.49
ClinPred		0.27	T
GERP RS		1.1
Varity_R		0.044
gMVP		0.23
Mutation Taster		=98/2	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: rs780114962; hg19: chr6-168434654;