rs55654273

Positions:

• chr9-83859200-T-C

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.3106A>G​(p.Asn1036Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 1,613,412 control chromosomes in the GnomAD database, including 14,901 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1036I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1458 hom., cov: 31)
  • Exomes 𝑓: 0.13 (13443 hom.)
• Consequence: KIF27 NM_017576.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038152337).
• BP6: Variant 9-83859200-T-C is Benign according to our data. Variant chr9-83859200-T-C is described in ClinVar as [Benign]. Clinvar id is 403013.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF27	NM_017576.4	c.3106A>G	p.Asn1036Asp	missense_variant	14/18	ENST00000297814.7
LOC124900638	XR_007061620.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF27	ENST00000297814.7	c.3106A>G	p.Asn1036Asp	missense_variant	14/18	1	NM_017576.4	P1
	ENST00000591217.5	n.879+40T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20339 AN: 152136 Hom.: 1451 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0925

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0925

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.115

GnomAD3 exomes AF: 0.122 AC: 30733 AN: 251410 Hom.: 2038 AF XY: 0.122 AC XY: 16526 AN XY: 135886

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.0988

Gnomad SAS exome AF: 0.0958

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.133 AC: 194067 AN: 1461158 Hom.: 13443 Cov.: 32 AF XY: 0.131 AC XY: 95565 AN XY: 726934

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0991

Gnomad4 SAS exome AF: 0.0939

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.139

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.134 AC: 20378 AN: 152254 Hom.: 1458 Cov.: 31 AF XY: 0.133 AC XY: 9935 AN XY: 74452

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0924

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0939

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.114

Alfa AF: 0.134 Hom.: 2294

Bravo AF: 0.129

TwinsUK AF: 0.135 AC: 499

ALSPAC AF: 0.134 AC: 517

ESP6500AA AF: 0.146 AC: 642

ESP6500EA AF: 0.137 AC: 1182

ExAC AF: 0.123 AC: 14904

Asia WGS AF: 0.100 AC: 349 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.127

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	0.073
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Benign	0.0016	T;.;.
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.068	T;T;T
MetaRNN	Benign	0.0038	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.40	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.43	T;T;T
Polyphen		0.020	B;B;B
Vest4		0.048
MPC		0.63
ClinPred		0.0013	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.069

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: rs55654273; hg19: chr9-86474115; COSMIC: COSV52826203; COSMIC: COSV52826203;