Variant 20-16367663-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000408042.5(KIF16B):c.3662A>G(p.Gln1221Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,612,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000086 ( 0 hom. )

Consequence

KIF16B
ENST00000408042.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.781

Variant links:

Genes affected

KIF16B (HGNC:15869): (kinesin family member 16B) The protein encoded by this gene is a kinesin-like protein that may be involved in intracellular trafficking. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2010]

KIF16B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.022289395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF16B	NM_024704.5 linkuse as main transcript	c.3498+2923A>G		intron_variant		ENST00000354981.7	NP_078980.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF16B	ENST00000408042.5 linkuse as main transcript	c.3662A>G	p.Gln1221Arg	missense_variant	23/23	1		ENSP00000384164		Q96L93-2
KIF16B	ENST00000354981.7 linkuse as main transcript	c.3498+2923A>G		intron_variant		1	NM_024704.5	ENSP00000347076	P1	Q96L93-1
KIF16B	ENST00000636835.1 linkuse as main transcript	c.3345+2923A>G		intron_variant		1		ENSP00000489838
KIF16B	ENST00000635823.2 linkuse as main transcript	c.4982A>G	p.Gln1661Arg	missense_variant	23/23	5		ENSP00000490639

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000999

AC:

AN:

240348

Hom.:

AF XY:

0.000129

AC XY:

AN XY:

131996

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000429

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000564

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000863

AC:

126

AN:

1460326

Hom.:

Cov.:

AF XY:

0.0000922

AC XY:

AN XY:

726434

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000112

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.3662A>G (p.Q1221R) alteration is located in exon 23 (coding exon 23) of the KIF16B gene. This alteration results from a A to G substitution at nucleotide position 3662, causing the glutamine (Q) at amino acid position 1221 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.71

MutationTaster

Benign

0.60

D;D;D;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.060

.;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

0.0

.;B

Vest4

0.056

MutPred

0.30

.;Loss of methylation at K1219 (P = 0.0618);

MVP

0.72

MPC

0.12

ClinPred

0.079

GERP RS

3.2

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over