rs13289566

Positions:

• chr9-83889090-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_017576.4(KIF27):​c.1973G>A​(p.Gly658Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,604,476 control chromosomes in the GnomAD database, including 30,432 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3509 hom., cov: 31)
  • Exomes 𝑓: 0.20 (26923 hom.)
• Consequence: KIF27 NM_017576.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023303032).
• BP6: Variant 9-83889090-C-T is Benign according to our data. Variant chr9-83889090-C-T is described in ClinVar as [Benign]. Clinvar id is 403015.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF27	NM_017576.4	c.1973G>A	p.Gly658Glu	missense_variant	7/18	ENST00000297814.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF27	ENST00000297814.7	c.1973G>A	p.Gly658Glu	missense_variant	7/18	1	NM_017576.4	P1
KIF27	ENST00000413982.5	c.1973G>A	p.Gly658Glu	missense_variant	7/17	1
KIF27	ENST00000334204.6	c.1973G>A	p.Gly658Glu	missense_variant	7/16	1
KIF27	ENST00000376347.1	c.146G>A	p.Gly49Glu	missense_variant	1/5	5

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32044 AN: 151600 Hom.: 3512 Cov.: 31

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.217

GnomAD3 exomes AF: 0.191 AC: 47664 AN: 249340 Hom.: 5187 AF XY: 0.199 AC XY: 26800 AN XY: 134764

Gnomad AFR exome AF: 0.243

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.000545

Gnomad SAS exome AF: 0.234

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.202

GnomAD4 exome AF: 0.204 AC: 296461 AN: 1452758 Hom.: 26923 Cov.: 31 AF XY: 0.206 AC XY: 148918 AN XY: 722944

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.000479

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.211 AC: 32047 AN: 151718 Hom.: 3509 Cov.: 31 AF XY: 0.211 AC XY: 15645 AN XY: 74132

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.214

Alfa AF: 0.220 Hom.: 1590

Bravo AF: 0.207

TwinsUK AF: 0.217 AC: 805

ALSPAC AF: 0.207 AC: 799

ESP6500AA AF: 0.250 AC: 1101

ESP6500EA AF: 0.217 AC: 1869

ExAC AF: 0.200 AC: 24236

Asia WGS AF: 0.0940 AC: 327 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.7
DANN	Benign	0.88
DEOGEN2	Benign	0.0028	T;.;.;.
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.68	T;T;T;T
MetaRNN	Benign	0.0023	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.29	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.080	N;N;N;N
REVEL	Benign	0.064
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	0.62	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.045
MPC		0.076
ClinPred		0.000014	T
GERP RS		0.39
Varity_R		0.046
gMVP		0.068

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

Other links and lift over

dbSNP: rs13289566; hg19: chr9-86504005; COSMIC: COSV52830489;