NM_017576.4:c.3106A>G

Variant names:

• chr9-83859200-T-C
• rs55654273
• NM_017576.4:c.3106A>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.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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1036S) has been classified as Likely benign.

• 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.06
• Publications: 13 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]

ENSG00000226877 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 403013.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF27	NM_017576.4	MANE Select	c.3106A>G	p.Asn1036Asp	missense	Exon 14 of 18	NP_060046.1	Q86VH2-1
	KIF27	NM_001271927.3		c.2908A>G	p.Asn970Asp	missense	Exon 13 of 17	NP_001258856.1	Q86VH2-2
	KIF27	NM_001271928.3		c.2815A>G	p.Asn939Asp	missense	Exon 12 of 16	NP_001258857.1	Q86VH2-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF27	ENST00000297814.7	TSL:1 MANE Select	c.3106A>G	p.Asn1036Asp	missense	Exon 14 of 18	ENSP00000297814.2	Q86VH2-1
	KIF27	ENST00000413982.5	TSL:1	c.2908A>G	p.Asn970Asp	missense	Exon 13 of 17	ENSP00000401688.1	Q86VH2-2
	KIF27	ENST00000334204.6	TSL:1	c.2815A>G	p.Asn939Asp	missense	Exon 12 of 16	ENSP00000333928.2	Q86VH2-3

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

GnomAD2 exomes AF: 0.122 AC: 30733 AN: 251410 AF XY: 0.122

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 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

African (AFR) AF: 0.142 AC: 4753 AN: 33446

American (AMR) AF: 0.0806 AC: 3604 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2873 AN: 26126

East Asian (EAS) AF: 0.0991 AC: 3932 AN: 39676

South Asian (SAS) AF: 0.0939 AC: 8097 AN: 86246

European-Finnish (FIN) AF: 0.164 AC: 8748 AN: 53412

Middle Eastern (MID) AF: 0.0553 AC: 319 AN: 5768

European-Non Finnish (NFE) AF: 0.139 AC: 154031 AN: 1111388

Other (OTH) AF: 0.128 AC: 7710 AN: 60372

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

African (AFR) AF: 0.143 AC: 5956 AN: 41556

American (AMR) AF: 0.0924 AC: 1414 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3470

East Asian (EAS) AF: 0.105 AC: 543 AN: 5182

South Asian (SAS) AF: 0.0939 AC: 453 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1752 AN: 10604

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

European-Non Finnish (NFE) AF: 0.139 AC: 9486 AN: 68004

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.135 Hom.: 3159

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

ClinVar submissions

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	0.073
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
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		2.1
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.43	T
Polyphen		0.020	B
Vest4		0.048
MPC		0.63
ClinPred		0.0013	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.069
Mutation Taster		=97/3	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: rs55654273; hg19: chr9-86474115; COSMIC: COSV52826203; COSMIC: COSV52826203;