20-16312412-C-A

Position:

• chr20-16312412-C-A

Variant summary

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

The NM_024704.5(KIF16B):​c.3718G>T​(p.Ala1240Ser) 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 NM_024704.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.180

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=0.1729865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF16B	NM_024704.5	c.3718G>T	p.Ala1240Ser	missense_variant	25/26	ENST00000354981.7	NP_078980.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF16B	ENST00000354981.7	c.3718G>T	p.Ala1240Ser	missense_variant	25/26	1	NM_024704.5	ENSP00000347076	P1
KIF16B	ENST00000636835.1	c.3565G>T	p.Ala1189Ser	missense_variant	24/25	1		ENSP00000489838

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Apr 13, 2022

The c.3718G>T (p.A1240S) alteration is located in exon 25 (coding exon 25) of the KIF16B gene. This alteration results from a G to T substitution at nucleotide position 3718, causing the alanine (A) at amino acid position 1240 to be replaced by a serine (S). 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	0.074
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.043	T;T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.85	T;D;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.27	N;.;.
MutationTaster	Benign	0.69	D;D;N
PROVEAN	Benign	-0.89	N;.;.
REVEL	Benign	0.048
Sift	Benign	0.067	T;.;.
Sift4G	Benign	0.23	T;.;T
Polyphen		0.027	B;.;.
Vest4		0.079
MutPred		0.55		Gain of phosphorylation at A1240 (P = 0.0571);.;.;
MVP		0.24
ClinPred		0.093	T
GERP RS		1.1
Varity_R		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-16293057;