rs12001918

Positions:

• chr9-83903881-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017576.4(KIF27):​c.637A>G​(p.Ile213Val) 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 1,613,850 control chromosomes in the GnomAD database, including 14,730 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.

• Frequency:
  • Genomes: 𝑓 0.13 (1444 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13286 hom.)
• Consequence: KIF27 NM_017576.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.16

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00205189).
• BP6: Variant 9-83903881-T-C is Benign according to our data. Variant chr9-83903881-T-C is described in ClinVar as [Benign]. Clinvar id is 403016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF27	NM_017576.4	c.637A>G	p.Ile213Val	missense_variant	4/18	ENST00000297814.7	NP_060046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF27	ENST00000297814.7	c.637A>G	p.Ile213Val	missense_variant	4/18	1	NM_017576.4	ENSP00000297814.2
KIF27	ENST00000413982.5	c.637A>G	p.Ile213Val	missense_variant	4/17	1		ENSP00000401688.1
KIF27	ENST00000334204.6	c.637A>G	p.Ile213Val	missense_variant	4/16	1		ENSP00000333928.2
KIF27	ENST00000495062.2	n.500-4077A>G		intron_variant		5		ENSP00000431390.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20309 AN: 152032 Hom.: 1437 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0934

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.122 AC: 30685 AN: 251380 Hom.: 2014 AF XY: 0.121 AC XY: 16507 AN XY: 135864

Gnomad AFR exome AF: 0.143

Gnomad AMR exome AF: 0.0784

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0988

Gnomad SAS exome AF: 0.0960

Gnomad FIN exome AF: 0.164

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.133 AC: 193915 AN: 1461700 Hom.: 13286 Cov.: 33 AF XY: 0.131 AC XY: 95505 AN XY: 727174

Gnomad4 AFR exome AF: 0.143

Gnomad4 AMR exome AF: 0.0806

Gnomad4 ASJ exome AF: 0.110

Gnomad4 EAS exome AF: 0.0994

Gnomad4 SAS exome AF: 0.0942

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.138

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.134 AC: 20348 AN: 152150 Hom.: 1444 Cov.: 32 AF XY: 0.133 AC XY: 9916 AN XY: 74390

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0922

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.112

Alfa AF: 0.133 Hom.: 3518

Bravo AF: 0.129

TwinsUK AF: 0.134 AC: 498

ALSPAC AF: 0.134 AC: 518

ESP6500AA AF: 0.146 AC: 644

ESP6500EA AF: 0.137 AC: 1181

ExAC AF: 0.123 AC: 14880

Asia WGS AF: 0.100 AC: 350 AN: 3478

EpiCase AF: 0.130

EpiControl AF: 0.127

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.099	T;.;.
Eigen	Benign	0.10
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.96	D;D;D
MetaRNN	Benign	0.0021	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.36	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.68	T;T;T
Sift4G	Benign	0.71	T;T;T
Polyphen		0.79	P;P;B
Vest4		0.15
MPC		0.15
ClinPred		0.019	T
GERP RS		4.4
Varity_R		0.067
gMVP		0.23

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: rs12001918; hg19: chr9-86518796; COSMIC: COSV52827746;