rs193920855

Positions:

• chr20-16427128-C-T

Variant summary

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

The NM_024704.5(KIF16B):​c.1588G>A​(p.Val530Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,456,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000035 (0 hom.)
• Consequence: KIF16B NM_024704.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -0.286

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=0.09137848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF16B	NM_024704.5	c.1588G>A	p.Val530Met	missense_variant	15/26	ENST00000354981.7	NP_078980.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF16B	ENST00000354981.7	c.1588G>A	p.Val530Met	missense_variant	15/26	1	NM_024704.5	ENSP00000347076.2
KIF16B	ENST00000408042.5	c.1588G>A	p.Val530Met	missense_variant	15/23	1		ENSP00000384164.1
KIF16B	ENST00000636835.1	c.1588G>A	p.Val530Met	missense_variant	15/25	1		ENSP00000489838.1
KIF16B	ENST00000635823.2	c.1588G>A	p.Val530Met	missense_variant	15/23	5		ENSP00000490639.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000162 AC: 4 AN: 247348 Hom.: 0 AF XY: 0.0000224 AC XY: 3 AN XY: 133636

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000672

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000350 AC: 51 AN: 1456130 Hom.: 0 Cov.: 31 AF XY: 0.0000345 AC XY: 25 AN XY: 724150

Gnomad4 AFR exome AF: 0.0000601

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000415

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.0000165 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.1
DANN	Benign	0.91
DEOGEN2	Benign	0.14	T;T;.
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.091	T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Benign	0.30	N;.;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.12	N;.;N
REVEL	Benign	0.18
Sift	Benign	0.28	T;.;T
Sift4G	Benign	0.13	T;.;T
Polyphen		0.0070	B;.;B
Vest4		0.029
MutPred		0.61		Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);Loss of helix (P = 0.2271);
MVP		0.57
MPC		0.12
ClinPred		0.032	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.037
gMVP		0.29

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

LitVar

Other links and lift over

dbSNP: rs193920855; hg19: chr20-16407773; COSMIC: COSV61701999;