20-16427128-C-A

Variant names:

• chr20-16427128-C-A
• rs193920855
• NM_024704.5:c.1588G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024704.5(KIF16B):​c.1588G>T​(p.Val530Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V530M) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KIF16B NM_024704.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08679718).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024704.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF16B	NM_024704.5	MANE Select	c.1588G>T	p.Val530Leu	missense	Exon 15 of 26	NP_078980.3
	KIF16B	NM_001410853.1		c.1588G>T	p.Val530Leu	missense	Exon 15 of 23	NP_001397782.1	A0A1B0GVS8
	KIF16B	NM_001199866.2		c.1588G>T	p.Val530Leu	missense	Exon 15 of 23	NP_001186795.1	Q96L93-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF16B	ENST00000354981.7	TSL:1 MANE Select	c.1588G>T	p.Val530Leu	missense	Exon 15 of 26	ENSP00000347076.2	Q96L93-1
	KIF16B	ENST00000408042.5	TSL:1	c.1588G>T	p.Val530Leu	missense	Exon 15 of 23	ENSP00000384164.1	Q96L93-2
	KIF16B	ENST00000636835.1	TSL:1	c.1588G>T	p.Val530Leu	missense	Exon 15 of 25	ENSP00000489838.1	A0A1B0GTU3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456130 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724150

African (AFR) AF: 0.00 AC: 0 AN: 33258

American (AMR) AF: 0.00 AC: 0 AN: 44042

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39562

South Asian (SAS) AF: 0.0000118 AC: 1 AN: 84872

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109244

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.2
DANN	Benign	0.90
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	0.10	N
PhyloP100		-0.29
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.24
Sift	Benign	0.077	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.54		Loss of catalytic residue at V530 (P = 0.0338)
MVP		0.48
MPC		0.11
ClinPred		0.070	T
GERP RS		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.075
gMVP		0.32
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs193920855; hg19: chr20-16407773;