12-75503942-C-T

Variant summary

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

The NM_007043.7(KRR1):​c.793G>A​(p.Glu265Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,611,880 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: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

KRR1
NM_007043.7 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.21
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]
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]

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 rank MANE Protein UniProt
KRR1NM_007043.7 linkc.793G>A p.Glu265Lys missense_variant Exon 7 of 10 ENST00000229214.9 NP_008974.5 Q13601-1
KRR1XM_047428133.1 linkc.499G>A p.Glu167Lys missense_variant Exon 7 of 10 XP_047284089.1
GLIPR1NM_006851.3 linkc.*4964C>T downstream_gene_variant ENST00000266659.8 NP_006842.2 P48060-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KRR1ENST00000229214.9 linkc.793G>A p.Glu265Lys missense_variant Exon 7 of 10 1 NM_007043.7 ENSP00000229214.4 Q13601-1
KRR1ENST00000438169.6 linkc.660+1256G>A intron_variant Intron 6 of 8 1 ENSP00000411740.2 Q13601-2
KRR1ENST00000551070.5 linkn.341G>A non_coding_transcript_exon_variant Exon 1 of 4 2
GLIPR1ENST00000266659.8 linkc.*4964C>T downstream_gene_variant 1 NM_006851.3 ENSP00000266659.3 P48060-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151932
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250950
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135648
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000274
AC:
40
AN:
1459948
Hom.:
0
Cov.:
30
AF XY:
0.0000262
AC XY:
19
AN XY:
726270
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000672
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:
0.0000306
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
151932
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74208
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000131
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
Alfa
AF:
0.0000868
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.793G>A (p.E265K) alteration is located in exon 7 (coding exon 7) of the KRR1 gene. This alteration results from a G to A substitution at nucleotide position 793, causing the glutamic acid (E) at amino acid position 265 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
0.21
BayesDel_addAF
Benign
-0.087
T
BayesDel_noAF
Benign
-0.38
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.25
T
Eigen
Benign
-0.077
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.8
N
REVEL
Benign
0.066
Sift
Benign
0.26
T
Sift4G
Benign
0.62
T
Polyphen
0.011
B
Vest4
0.58
MutPred
0.29
Gain of methylation at E265 (P = 0.001);
MVP
0.42
MPC
0.096
ClinPred
0.44
T
GERP RS
4.8
Varity_R
0.16
gMVP
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.22
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.22
Position offset: -38

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.

Other links and lift over

dbSNP: rs1338119127; hg19: chr12-75897722; API