rs58077086

Positions:

• chr9-83850216-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.3439A>G​(p.Met1147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,611,616 control chromosomes in the GnomAD database, including 42,729 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 0.18 (2906 hom., cov: 31)
  • Exomes 𝑓: 0.23 (39823 hom.)
• Consequence: KIF27 NM_017576.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.266

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=0.0017277896).
• BP6: Variant 9-83850216-T-C is Benign according to our data. Variant chr9-83850216-T-C is described in ClinVar as [Benign]. Clinvar id is 403011.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF27	NM_017576.4	c.3439A>G	p.Met1147Val	missense_variant	16/18	ENST00000297814.7
LOC124900638	XR_007061620.1	n.263+625T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF27	ENST00000297814.7	c.3439A>G	p.Met1147Val	missense_variant	16/18	1	NM_017576.4	P1
	ENST00000591217.5	n.582+625T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26623 AN: 152078 Hom.: 2900 Cov.: 31

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.187

GnomAD3 exomes AF: 0.199 AC: 49852 AN: 251066 Hom.: 5449 AF XY: 0.202 AC XY: 27428 AN XY: 135694

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.174

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.104

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.201

Gnomad NFE exome AF: 0.243

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.229 AC: 334515 AN: 1459420 Hom.: 39823 Cov.: 31 AF XY: 0.228 AC XY: 165770 AN XY: 726192

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.179

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.120

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.216

GnomAD4 genome AF: 0.175 AC: 26635 AN: 152196 Hom.: 2906 Cov.: 31 AF XY: 0.172 AC XY: 12781 AN XY: 74396

Gnomad4 AFR AF: 0.0528

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.190

Alfa AF: 0.225 Hom.: 1301

Bravo AF: 0.170

ESP6500AA AF: 0.0563 AC: 248

ESP6500EA AF: 0.241 AC: 2071

ExAC AF: 0.196 AC: 23828

EpiCase AF: 0.245

EpiControl AF: 0.245

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	0.062
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	1.2
DANN	Benign	0.79
DEOGEN2	Benign	0.0054	T;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.69	T;T;T
MetaRNN	Benign	0.0017	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.090
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.19	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.034
MPC		0.56
ClinPred		0.0017	T
GERP RS		-0.82
Varity_R		0.076
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

Other links and lift over

dbSNP: rs58077086; hg19: chr9-86465131; COSMIC: COSV52830200; COSMIC: COSV52830200;