Variant chr9-83837086-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017576.4(KIF27):c.4121G>A(p.Arg1374Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KIF27
NM_017576.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

KIF27 (HGNC:18632): (kinesin family member 27) This gene is a member of the KIF27 (kinesin 4) sub-family of the mammalian kinesin family. The gene is an ortholog of the Drosophila Cos2 gene, which plays an important role in the Hedgehog signaling pathway. The encoded protein contains an N-terminal motor domain which includes nucleotide-binding and microtubule-interacting regions, a stalk domain containing a predicted coiled coil motif and a C-terminal tail domain. Alternatively spliced transcript variants have been observed for this gene. Pseudogenes associated with this gene are located on chromosome 9. [provided by RefSeq, Dec 2012]

KIF27 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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=0.2202481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF27	NM_017576.4 linkuse as main transcript	c.4121G>A	p.Arg1374Gln	missense_variant	18/18	ENST00000297814.7
LOC101927552	XR_001746793.2 linkuse as main transcript	n.2449C>T		non_coding_transcript_exon_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF27	ENST00000297814.7 linkuse as main transcript	c.4121G>A	p.Arg1374Gln	missense_variant	18/18	1	NM_017576.4	P1	Q86VH2-1
	ENST00000591217.5 linkuse as main transcript	n.239C>T		non_coding_transcript_exon_variant	3/8	5
	ENST00000650551.1 linkuse as main transcript	n.758C>T		non_coding_transcript_exon_variant	7/8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461670

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.4121G>A (p.R1374Q) alteration is located in exon 18 (coding exon 17) of the KIF27 gene. This alteration results from a G to A substitution at nucleotide position 4121, causing the arginine (R) at amino acid position 1374 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Uncertain

0.032

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.016

T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Uncertain

-0.048

MutationAssessor

Uncertain

2.5

M;.;.

MutationTaster

Benign

0.62

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;P

Vest4

0.23

MutPred

0.54

Loss of MoRF binding (P = 0.0222);.;.;

MVP

0.68

MPC

2.9

ClinPred

0.99

GERP RS

2.8

Varity_R

0.30

gMVP

0.64

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over