20-16367645-A-G

Position:

• chr20-16367645-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000408042.5(KIF16B):​c.3680T>C​(p.Met1227Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF16B ENST00000408042.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39805186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF16B	NM_024704.5	c.3498+2941T>C		intron_variant		ENST00000354981.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF16B	ENST00000408042.5	c.3680T>C	p.Met1227Thr	missense_variant	23/23	1
KIF16B	ENST00000354981.7	c.3498+2941T>C		intron_variant		1	NM_024704.5	P1
KIF16B	ENST00000636835.1	c.3345+2941T>C		intron_variant		1
KIF16B	ENST00000635823.2	c.5000T>C	p.Met1667Thr	missense_variant	23/23	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000831 AC: 2 AN: 240614 Hom.: 0 AF XY: 0.00000757 AC XY: 1 AN XY: 132138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

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 Cov.: 32

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000860 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2023

The c.3680T>C (p.M1227T) alteration is located in exon 23 (coding exon 23) of the KIF16B gene. This alteration results from a T to C substitution at nucleotide position 3680, causing the methionine (M) at amino acid position 1227 to be replaced by a threonine (T). 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	-0.26	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.97
Eigen	Benign	0.089
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.35	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.40	T;T
MetaSVM	Benign	-0.95	T
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.070	.;N
REVEL	Benign	0.28
Sift	Uncertain	0.0010	.;D
Sift4G	Uncertain	0.0060	.;D
Polyphen		0.11	.;B
Vest4		0.22
MutPred		0.47		.;Loss of helix (P = 0.0167);
MVP		0.79
MPC		0.13
ClinPred		0.93	D
GERP RS		5.2
gMVP		0.26

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

Other links and lift over

dbSNP: rs749801543; hg19: chr20-16348290;