Variant 16-19714173-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012991.3(KNOP1):c.863G>A(p.Arg288Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

KNOP1
NM_001012991.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.236

Variant links:

Genes affected

KNOP1 (HGNC:34404): (lysine rich nucleolar protein 1) The protein encoded by this gene is a nucleolar protein that interacts with zinc finger 106 protein. The encoded protein has several of the same characteristics as nucleostemin and may be involved in testis development. [provided by RefSeq, Feb 2017]

KNOP1 links:

KNOP1 (HGNC:):

KNOP1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050213158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNOP1	NM_001012991.3 linkuse as main transcript	c.863G>A	p.Arg288Lys	missense_variant	2/5	ENST00000219837.12	NP_001013009.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KNOP1	ENST00000219837.12 linkuse as main transcript	c.863G>A	p.Arg288Lys	missense_variant	2/5	1	NM_001012991.3	ENSP00000219837.7	Q1ED39
KNOP1	ENST00000567367.1 linkuse as main transcript	c.404G>A	p.Arg135Lys	missense_variant	1/3	3		ENSP00000455369.1	H3BPL4
KNOP1	ENST00000565844.1 linkuse as main transcript	n.943G>A		non_coding_transcript_exon_variant	2/4	5
ENSG00000261312	ENST00000565916.1 linkuse as main transcript	n.782-613C>T		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461072

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2024

The c.863G>A (p.R288K) alteration is located in exon 2 (coding exon 1) of the KNOP1 gene. This alteration results from a G to A substitution at nucleotide position 863, causing the arginine (R) at amino acid position 288 to be replaced by a lysine (K). 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

0.085

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.5

DANN

Benign

0.96

DEOGEN2

Benign

0.0068

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.54

M_CAP

Benign

0.0033

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.62

REVEL

Benign

0.11

Sift

Benign

0.56

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.11

MutPred

0.27

Gain of methylation at R288 (P = 0.0126);

MVP

0.32

MPC

0.092

ClinPred

0.070

GERP RS

1.6

Varity_R

0.054

gMVP

0.026

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over