9-83853800-A-T

Variant names:

• chr9-83853800-A-T
• rs295274
• NM_017576.4:c.3186T>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_017576.4(KIF27):​c.3186T>A​(p.Ile1062Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,611,514 control chromosomes in the GnomAD database, including 338,568 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (35243 hom., cov: 31)
  • Exomes 𝑓: 0.64 (303325 hom.)
• Consequence: KIF27 NM_017576.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.594
• Publications: 18 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 9-83853800-A-T is Benign according to our data. Variant chr9-83853800-A-T is described in ClinVar as Benign. ClinVar VariationId is 403012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.594 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.795 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.3186T>A	p.Ile1062Ile	synonymous	Exon 15 of 18	NP_060046.1
	KIF27	NM_001271927.3		c.2988T>A	p.Ile996Ile	synonymous	Exon 14 of 17	NP_001258856.1
	KIF27	NM_001271928.3		c.2895T>A	p.Ile965Ile	synonymous	Exon 13 of 16	NP_001258857.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF27	ENST00000297814.7	TSL:1 MANE Select	c.3186T>A	p.Ile1062Ile	synonymous	Exon 15 of 18	ENSP00000297814.2
	KIF27	ENST00000413982.5	TSL:1	c.2988T>A	p.Ile996Ile	synonymous	Exon 14 of 17	ENSP00000401688.1
	KIF27	ENST00000334204.6	TSL:1	c.2895T>A	p.Ile965Ile	synonymous	Exon 13 of 16	ENSP00000333928.2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102257 AN: 151916 Hom.: 35181 Cov.: 31

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.648

GnomAD2 exomes AF: 0.620 AC: 155598 AN: 250842 AF XY: 0.628

Gnomad AFR exome AF: 0.806

Gnomad AMR exome AF: 0.405

Gnomad ASJ exome AF: 0.650

Gnomad EAS exome AF: 0.506

Gnomad FIN exome AF: 0.693

Gnomad NFE exome AF: 0.651

Gnomad OTH exome AF: 0.621

GnomAD4 exome AF: 0.642 AC: 936623 AN: 1459480 Hom.: 303325 Cov.: 37 AF XY: 0.642 AC XY: 466563 AN XY: 726214

African (AFR) AF: 0.813 AC: 27200 AN: 33436

American (AMR) AF: 0.419 AC: 18745 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16804 AN: 26110

East Asian (EAS) AF: 0.531 AC: 21077 AN: 39668

South Asian (SAS) AF: 0.661 AC: 56949 AN: 86216

European-Finnish (FIN) AF: 0.699 AC: 37299 AN: 53394

Middle Eastern (MID) AF: 0.641 AC: 3689 AN: 5752

European-Non Finnish (NFE) AF: 0.645 AC: 715888 AN: 1109890

Other (OTH) AF: 0.646 AC: 38972 AN: 60316

GnomAD4 genome AF: 0.673 AC: 102378 AN: 152034 Hom.: 35243 Cov.: 31 AF XY: 0.672 AC XY: 49949 AN XY: 74308

African (AFR) AF: 0.803 AC: 33312 AN: 41506

American (AMR) AF: 0.519 AC: 7920 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2220 AN: 3466

East Asian (EAS) AF: 0.519 AC: 2676 AN: 5158

South Asian (SAS) AF: 0.638 AC: 3068 AN: 4808

European-Finnish (FIN) AF: 0.694 AC: 7328 AN: 10560

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43762 AN: 67948

Other (OTH) AF: 0.651 AC: 1374 AN: 2112

Alfa AF: 0.631 Hom.: 8041

Bravo AF: 0.663

Asia WGS AF: 0.595 AC: 2068 AN: 3478

EpiCase AF: 0.641

EpiControl AF: 0.646

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
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.2
DANN	Benign	0.78
PhyloP100		0.59
Mutation Taster		=100/0	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: rs295274; hg19: chr9-86468715; COSMIC: COSV52827647; COSMIC: COSV52827647;