rs20455

Variant names:

• chr6-39357302-A-G
• rs20455
• NM_145027.6:c.2155T>C
• KIF6 p.Trp719Arg

Your query was ambiguous. Multiple possible variants found:

• chr6-39357302-A-G
• chr6-39357302-A-C
• chr6-39357302-A-T

GermlineCancer (beta)

Variant summary

Our verdict is

Benign

-9 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -9 classification points (ACMG Germline Pathogenicity v2019): 0P and 9B. BA1BP4

The NM_145027.6(KIF6):c.2155T>C (p.Trp719Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.386 (AC=622,475) in the gnomAD database across 1,611,174 control chromosomes, including 129,068 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.803. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain Significance (★★★). This exact variant is curated in the UniProt human variants database as Uncertain Significance; it is also listed as a COSMIC curated somatic variant.

• Frequency:
  • Genomes: 𝑓 0.49 (21098 hom., cov: 31)
  • Exomes 𝑓: 0.38 (107970 hom.)
• Consequence: KIF6 NM_145027.6 missense
• Clinical Significance: drug response reviewed by expert panel O:1
• Conservation: PhyloP100: 0.0610
• Publications: 136 publications found

Genes affected

KIF6 (HGNC:21202): (kinesin family member 6) This gene encodes a member of a family of molecular motors which are involved in intracellular transport of protein complexes, membrane organelles, and messenger ribonucleic acid along microtubules. Kinesins function as homodimeric molecules with two N-terminal head domains that move along microtubules and two C-terminal tail domains that interact with the transported cargo, either directly or indirectly, through adapter molecules. This gene is ubiquitously expressed in coronary arteries and other vascular tissue. A naturally occurring mutation in this gene is associated with coronary heart disease. [provided by RefSeq, May 2017]

KIF6 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: LiferaOmics

LOC107986594 (HGNC:):

Classification according to ACMG Germline Pathogenicity v2019

Our verdict: Benign. The variant received -9 points.

• BP4: Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Supporting).
• BA1: GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.8033 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_145027.6. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	NM_145027.6	MANE Select	c.2155T>C	p.Trp719Arg	missense	Exon 19 of 23	NP_659464.3
	KIF6	NM_001289020.3		c.2104T>C	p.Trp702Arg	missense	Exon 18 of 22	NP_001275949.1
	KIF6	NM_001289021.3		c.1987T>C	p.Trp663Arg	missense	Exon 18 of 22	NP_001275950.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF6	ENST00000287152.12	TSL:2 MANE Select	c.2155T>C	p.Trp719Arg	missense	Exon 19 of 23	ENSP00000287152.7	Q6ZMV9-1
	KIF6	ENST00000458470.5	TSL:1	c.1828T>C	p.Trp610Arg	missense	Exon 16 of 19	ENSP00000409417.1	H0Y718
	KIF6	ENST00000229913.9	TSL:1	c.508T>C	p.Trp170Arg	missense	Exon 6 of 10	ENSP00000229913.5	Q6ZMV9-2

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74283 AN: 151892 Hom.: 21067 Cov.: 31

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.468

GnomAD2 exomes AF: 0.405 AC: 101846 AN: 251262 AF XY: 0.400

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.349

Gnomad EAS exome AF: 0.467

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.393

GnomAD4 exome AF: 0.376 AC: 548109 AN: 1459164 Hom.: 107970 Cov.: 32 AF XY: 0.376 AC XY: 273110 AN XY: 726034

African (AFR) AF: 0.811 AC: 27109 AN: 33412

American (AMR) AF: 0.344 AC: 15356 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 8875 AN: 26120

East Asian (EAS) AF: 0.477 AC: 18909 AN: 39680

South Asian (SAS) AF: 0.428 AC: 36887 AN: 86146

European-Finnish (FIN) AF: 0.345 AC: 18432 AN: 53396

Middle Eastern (MID) AF: 0.414 AC: 2387 AN: 5764

European-Non Finnish (NFE) AF: 0.357 AC: 395811 AN: 1109676

Other (OTH) AF: 0.404 AC: 24343 AN: 60290

GnomAD4 genome AF: 0.489 AC: 74366 AN: 152010 Hom.: 21098 Cov.: 31 AF XY: 0.485 AC XY: 36000 AN XY: 74288

African (AFR) AF: 0.798 AC: 33085 AN: 41462

American (AMR) AF: 0.385 AC: 5875 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1176 AN: 3472

East Asian (EAS) AF: 0.477 AC: 2454 AN: 5142

South Asian (SAS) AF: 0.445 AC: 2143 AN: 4818

European-Finnish (FIN) AF: 0.347 AC: 3667 AN: 10578

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24541 AN: 67962

Other (OTH) AF: 0.470 AC: 992 AN: 2112

Alfa AF: 0.424 Hom.: 38444

Bravo AF: 0.504

Asia WGS AF: 0.512 AC: 1782 AN: 3478

EpiCase AF: 0.368

EpiControl AF: 0.371

Local populations

ToMMo 61KJPN (+60KJPN MNV) AF: 0.490 AC: 60123 AN: 122746

Turkish Variome AF: 0.371 AC: 2485 AN: 6698 Hom.: 481

WBBC (Westlake BioBank for Chinese) pilot AF: 0.460 AC: 4124 AN: 8960 Hom.: 946

ABraOM SABE-WGS-1171 AF: 0.453 AC: 1060 AN: 2342 Hom.: 253

ClinVar

ClinVar submissions

Significance: drug response

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	-	pravastatin response - Efficacy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.0
DANN	Benign	0.30
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.00095	N
LIST_S2	Benign	0.032	T
MetaRNN	Benign	8.2e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.81	N
PhyloP100		0.061
PrimateAI	Benign	0.17	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.23
Sift	Benign	0.69	T
Sift4G	Benign	0.36	T
Varity_R		0.051
gMVP		0.28
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs20455;

hg19: chr6-39325078;

COSMIC: COSV54671370;

COSMIC: COSV54671370;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar