20-16367550-A-G

Position:

• chr20-16367550-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000408042.5(KIF16B):​c.3775T>C​(p.Ser1259Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/18 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: -0.891

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1195105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF16B	NM_024704.5	c.3498+3036T>C		intron_variant		ENST00000354981.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF16B	ENST00000408042.5	c.3775T>C	p.Ser1259Pro	missense_variant	23/23	1
KIF16B	ENST00000354981.7	c.3498+3036T>C		intron_variant		1	NM_024704.5	P1
KIF16B	ENST00000636835.1	c.3345+3036T>C		intron_variant		1
KIF16B	ENST00000635823.2	c.5095T>C	p.Ser1699Pro	missense_variant	23/23	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Aug 30, 2021

The c.3775T>C (p.S1259P) 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 3775, causing the serine (S) at amino acid position 1259 to be replaced by a proline (P). 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	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.15
DANN	Benign	0.78
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
Polyphen		0.0	.;B
Vest4		0.032
MutPred		0.28		.;Loss of catalytic residue at S1259 (P = 0.0132);
MVP		0.17
MPC		0.14
ClinPred		0.72	D
GERP RS		-11
gMVP		0.13

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: rs2064702678; hg19: chr20-16348195;