Variant 16-19714437-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 ENST00000219837.12(KNOP1):c.599G>A(p.Arg200Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

KNOP1
ENST00000219837.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.363

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:

(HGNC:):

links:

Genome browser will be placed here

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=0.05445403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNOP1	NM_001012991.3 linkuse as main transcript	c.599G>A	p.Arg200Gln	missense_variant	2/5	ENST00000219837.12	NP_001013009.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KNOP1	ENST00000219837.12 linkuse as main transcript	c.599G>A	p.Arg200Gln	missense_variant	2/5	1	NM_001012991.3	ENSP00000219837	P2
	ENST00000565916.1 linkuse as main transcript	n.782-349C>T		intron_variant, non_coding_transcript_variant		5
KNOP1	ENST00000567367.1 linkuse as main transcript	c.143G>A	p.Arg48Gln	missense_variant	1/3	3		ENSP00000455369
KNOP1	ENST00000565844.1 linkuse as main transcript	n.679G>A		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000360

AC:

AN:

250304

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74200

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000106

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000495

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Feb 01, 2023

The c.599G>A (p.R200Q) 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 599, causing the arginine (R) at amino acid position 200 to be replaced by a glutamine (Q). 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

0.077

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.60

M_CAP

Benign

0.0073

MetaRNN

Benign

0.054

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

MutationTaster

Benign

0.97

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.4

REVEL

Benign

0.032

Sift

Benign

0.18

Sift4G

Benign

0.45

Polyphen

0.45

Vest4

0.12

MVP

0.16

MPC

0.42

ClinPred

0.13

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.024

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over