rs12001918

Variant names:

• chr9-83903881-T-C
• rs12001918
• NM_017576.4:c.637A>G

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• 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
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF27	NM_017576.4	MANE Select	c.637A>G	p.Ile213Val	missense	Exon 4 of 18	NP_060046.1
	KIF27	NM_001271927.3		c.637A>G	p.Ile213Val	missense	Exon 4 of 17	NP_001258856.1
	KIF27	NM_001271928.3		c.637A>G	p.Ile213Val	missense	Exon 4 of 16	NP_001258857.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF27	ENST00000297814.7	TSL:1 MANE Select	c.637A>G	p.Ile213Val	missense	Exon 4 of 18	ENSP00000297814.2
	KIF27	ENST00000413982.5	TSL:1	c.637A>G	p.Ile213Val	missense	Exon 4 of 17	ENSP00000401688.1
	KIF27	ENST00000334204.6	TSL:1	c.637A>G	p.Ile213Val	missense	Exon 4 of 16	ENSP00000333928.2

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

GnomAD2 exomes AF: 0.122 AC: 30685 AN: 251380 AF XY: 0.121

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 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

African (AFR) AF: 0.143 AC: 4776 AN: 33480

American (AMR) AF: 0.0806 AC: 3603 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2873 AN: 26136

East Asian (EAS) AF: 0.0994 AC: 3946 AN: 39698

South Asian (SAS) AF: 0.0942 AC: 8122 AN: 86258

European-Finnish (FIN) AF: 0.164 AC: 8748 AN: 53410

Middle Eastern (MID) AF: 0.0557 AC: 321 AN: 5768

European-Non Finnish (NFE) AF: 0.138 AC: 153814 AN: 1111834

Other (OTH) AF: 0.128 AC: 7712 AN: 60392

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

African (AFR) AF: 0.144 AC: 5971 AN: 41522

American (AMR) AF: 0.0922 AC: 1410 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3468

East Asian (EAS) AF: 0.105 AC: 542 AN: 5176

South Asian (SAS) AF: 0.0948 AC: 456 AN: 4812

European-Finnish (FIN) AF: 0.164 AC: 1737 AN: 10582

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9463 AN: 67988

Other (OTH) AF: 0.112 AC: 236 AN: 2108

Alfa AF: 0.133 Hom.: 4592

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.36	N
PhyloP100		2.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.22
Sift	Benign	0.68	T
Sift4G	Benign	0.71	T
Polyphen		0.79	P
Vest4		0.15
MPC		0.15
ClinPred		0.019	T
GERP RS		4.4
Varity_R		0.067
gMVP		0.23
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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