20-16356379-T-C

Position:

• chr20-16356379-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024704.5(KIF16B):​c.3572A>G​(p.Tyr1191Cys) 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 pathogenic 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: 7.27

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF16B	NM_024704.5	c.3572A>G	p.Tyr1191Cys	missense_variant	23/26	ENST00000354981.7	NP_078980.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF16B	ENST00000354981.7	c.3572A>G	p.Tyr1191Cys	missense_variant	23/26	1	NM_024704.5	ENSP00000347076	P1
KIF16B	ENST00000636835.1	c.3419A>G	p.Tyr1140Cys	missense_variant	22/25	1		ENSP00000489838

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.59	D;T;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Uncertain	0.23	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	M;.;.
MutationTaster	Benign	1.0	D;D;D
PROVEAN	Pathogenic	-6.3	D;.;.
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D;.;.
Sift4G	Pathogenic	0.0010	D;.;D
Polyphen		1.0	D;.;.
Vest4		0.94
MutPred		0.64		Loss of sheet (P = 3e-04);.;.;
MVP		0.67
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1555853632; hg19: chr20-16337024;