20-16312378-T-C

Position:

• chr20-16312378-T-C

Variant summary

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

The NM_024704.5(KIF16B):​c.3752A>G​(p.Asn1251Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 6.61

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 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
KIF16B	NM_024704.5	c.3752A>G	p.Asn1251Ser	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.3752A>G	p.Asn1251Ser	missense_variant	25/26	1	NM_024704.5	ENSP00000347076	P1
KIF16B	ENST00000636835.1	c.3599A>G	p.Asn1200Ser	missense_variant	24/25	1		ENSP00000489838

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

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

Jul 15, 2021

The c.3752A>G (p.N1251S) alteration is located in exon 25 (coding exon 25) of the KIF16B gene. This alteration results from a A to G substitution at nucleotide position 3752, causing the asparagine (N) at amino acid position 1251 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	0.29
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;T;.
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	1.9	L;.;.
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Benign	-1.5	N;.;.
REVEL	Benign	0.26
Sift	Benign	0.21	T;.;.
Sift4G	Benign	0.55	T;.;D
Polyphen		1.0	D;.;.
Vest4		0.34
MutPred		0.53		Gain of catalytic residue at K1252 (P = 0.0343);.;.;
MVP		0.55
ClinPred		0.87	D
GERP RS		5.6
Varity_R		0.21

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: rs1168225470; hg19: chr20-16293023;