Variant chr9-83842387-C-A 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.3571G>T(p.Gly1191Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIF27
NM_017576.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.167

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=0.12176797).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF27	NM_017576.4 linkuse as main transcript	c.3571G>T	p.Gly1191Cys	missense_variant	17/18	ENST00000297814.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF27	ENST00000297814.7 linkuse as main transcript	c.3571G>T	p.Gly1191Cys	missense_variant	17/18	1	NM_017576.4	P1	Q86VH2-1
KIF27	ENST00000413982.5 linkuse as main transcript	c.3373G>T	p.Gly1125Cys	missense_variant	16/17	1			Q86VH2-2
KIF27	ENST00000334204.6 linkuse as main transcript	c.3280G>T	p.Gly1094Cys	missense_variant	15/16	1			Q86VH2-3
	ENST00000591217.5 linkuse as main transcript	n.362+3578C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000294

AC:

AN:

1358476

Hom.:

Cov.:

AF XY:

0.00000299

AC XY:

AN XY:

669338

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:

0.0000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000281

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

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

Aug 04, 2023

The c.3571G>T (p.G1191C) alteration is located in exon 17 (coding exon 16) of the KIF27 gene. This alteration results from a G to T substitution at nucleotide position 3571, causing the glycine (G) at amino acid position 1191 to be replaced by a cysteine (C). 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

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

T;.;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-5.0

D;D;D

REVEL

Benign

0.074

Sift

Benign

0.033

D;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.0090

B;B;B

Vest4

0.26

MutPred

0.48

Loss of loop (P = 0.1258);.;.;

MVP

0.47

MPC

0.62

ClinPred

0.86

GERP RS

0.97

Varity_R

0.31

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over