Variant chr12-75511533-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007043.7(KRR1):c.65A>G(p.Lys22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 6.8e-7 ( 0 hom. )

Consequence

KRR1
NM_007043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Variant links:

Genes affected

KRR1 (HGNC:5176): (KRR1 small subunit processome component homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in chromosome; intercellular bridge; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

KRR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18500057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRR1	NM_007043.7 linkuse as main transcript	c.65A>G	p.Lys22Arg	missense_variant	1/10	ENST00000229214.9
KRR1	XM_047428133.1 linkuse as main transcript	c.-265A>G		5_prime_UTR_variant	1/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRR1	ENST00000229214.9 linkuse as main transcript	c.65A>G	p.Lys22Arg	missense_variant	1/10	1	NM_007043.7	P1	Q13601-1
KRR1	ENST00000438169.6 linkuse as main transcript	c.65A>G	p.Lys22Arg	missense_variant	1/9	1			Q13601-2
KRR1	ENST00000550023.5 linkuse as main transcript	n.81A>G		non_coding_transcript_exon_variant	1/4	2
KRR1	ENST00000550898.1 linkuse as main transcript	n.104A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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 04, 2022

The c.65A>G (p.K22R) alteration is located in exon 1 (coding exon 1) of the KRR1 gene. This alteration results from a A to G substitution at nucleotide position 65, causing the lysine (K) at amino acid position 22 to be replaced by an arginine (R). 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

0.080

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.3

M;M

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.57

N;N

REVEL

Benign

0.12

Sift

Benign

0.074

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.020

B;.

Vest4

0.30

MutPred

0.15

Loss of ubiquitination at K22 (P = 0.0059);Loss of ubiquitination at K22 (P = 0.0059);

MVP

0.66

MPC

0.068

ClinPred

0.58

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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