Genetic Variant KRR1:p.Glu365Lys (chr12-75499862-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_007043.7(KRR1):c.1093G>A(p.Glu365Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

KRR1
NM_007043.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

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:

GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

GLIPR1 links:

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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=0.21811157).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRR1	NM_007043.7 link	c.1093G>A	p.Glu365Lys	missense_variant	Exon 10 of 10	ENST00000229214.9	NP_008974.5	Q13601-1
GLIPR1	NM_006851.3 link	c.*884C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000266659.8	NP_006842.2	P48060-1
KRR1	XM_047428133.1 link	c.799G>A	p.Glu267Lys	missense_variant	Exon 10 of 10		XP_047284089.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KRR1	ENST00000229214.9 link	c.1093G>A	p.Glu365Lys	missense_variant	Exon 10 of 10	1	NM_007043.7	ENSP00000229214.4	Q13601-1
KRR1	ENST00000438169.6 link	c.922G>A	p.Glu308Lys	missense_variant	Exon 9 of 9	1		ENSP00000411740.2	Q13601-2
GLIPR1	ENST00000266659.8 link	c.*884C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_006851.3	ENSP00000266659.3	P48060-1
KRR1	ENST00000551070.5 link	n.641G>A		non_coding_transcript_exon_variant	Exon 4 of 4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1455874

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724292

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000361

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

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1093G>A (p.E365K) alteration is located in exon 10 (coding exon 10) of the KRR1 gene. This alteration results from a G to A substitution at nucleotide position 1093, causing the glutamic acid (E) at amino acid position 365 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

0.20

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.86

MutationAssessor

Benign

1.5

L;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.018

D;D

Sift4G

Benign

0.58

T;T

Polyphen

0.98

D;.

Vest4

0.24

MutPred

0.32

Gain of MoRF binding (P = 0.0026);.;

MVP

0.59

MPC

0.28

ClinPred

0.89

GERP RS

5.5

Varity_R

0.15

gMVP

0.15

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

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