Variant 12-75506889-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_007043.7(KRR1):c.286G>A(p.Glu96Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,222 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

KRR1
NM_007043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.40

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRR1	NM_007043.7 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	3/10	ENST00000229214.9
KRR1	XM_047428133.1 linkuse as main transcript	c.-9G>A		5_prime_UTR_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRR1	ENST00000229214.9 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	3/10	1	NM_007043.7	P1	Q13601-1
KRR1	ENST00000438169.6 linkuse as main transcript	c.286G>A	p.Glu96Lys	missense_variant	3/9	1			Q13601-2
KRR1	ENST00000550023.5 linkuse as main transcript	n.302G>A		non_coding_transcript_exon_variant	3/4	2
KRR1	ENST00000550898.1 linkuse as main transcript	n.325G>A		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152060

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000642

AC:

AN:

249178

Hom.:

AF XY:

0.0000816

AC XY:

AN XY:

134772

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:

0.000330

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.0000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1460044

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

726256

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:

0.000337

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00000900

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74404

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:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000231

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000110

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

Nov 30, 2022

The c.286G>A (p.E96K) alteration is located in exon 3 (coding exon 3) of the KRR1 gene. This alteration results from a G to A substitution at nucleotide position 286, causing the glutamic acid (E) at amino acid position 96 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

D;.

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.058

MetaRNN

Uncertain

0.54

D;D

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.6

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.39

Sift

Benign

0.048

D;D

Sift4G

Uncertain

0.021

D;D

Polyphen

0.99

D;.

Vest4

0.84

MVP

0.57

MPC

0.30

ClinPred

0.73

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.57

gMVP

0.84

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