20-16335933-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024704.5(KIF16B):ā€‹c.3704A>Gā€‹(p.Tyr1235Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000944 in 1,588,364 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000077 ( 0 hom. )

Consequence

KIF16B
NM_024704.5 missense

Scores

3
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.60
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF16BNM_024704.5 linkuse as main transcriptc.3704A>G p.Tyr1235Cys missense_variant 24/26 ENST00000354981.7 NP_078980.3 Q96L93-1A0A140VK74

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF16BENST00000354981.7 linkuse as main transcriptc.3704A>G p.Tyr1235Cys missense_variant 24/261 NM_024704.5 ENSP00000347076.2 Q96L93-1
KIF16BENST00000636835.1 linkuse as main transcriptc.3551A>G p.Tyr1184Cys missense_variant 23/251 ENSP00000489838.1 A0A1B0GTU3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152242
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000403
AC:
1
AN:
247914
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
134158
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000766
AC:
11
AN:
1436122
Hom.:
0
Cov.:
26
AF XY:
0.00000838
AC XY:
6
AN XY:
716198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000101
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152242
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74390
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0

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 submitterclinical testingAmbry GeneticsOct 06, 2024The c.3704A>G (p.Y1235C) alteration is located in exon 24 (coding exon 24) of the KIF16B gene. This alteration results from a A to G substitution at nucleotide position 3704, causing the tyrosine (Y) at amino acid position 1235 to be replaced by a cysteine (C). 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
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.025
T
BayesDel_noAF
Benign
-0.27
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.48
T;T;.
Eigen
Pathogenic
0.70
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Uncertain
0.71
D;D;D
MetaSVM
Benign
-0.51
T
MutationAssessor
Uncertain
2.3
M;.;.
PROVEAN
Pathogenic
-6.1
D;.;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0010
D;.;.
Sift4G
Uncertain
0.0030
D;.;D
Polyphen
1.0
D;.;.
Vest4
0.64
MVP
0.62
ClinPred
0.99
D
GERP RS
5.1
Varity_R
0.68

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.

Other links and lift over

dbSNP: rs143212144; hg19: chr20-16316578; API