chr12-75506341-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_007043.7(KRR1):c.578T>C(p.Ile193Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
KRR1
NM_007043.7 missense
NM_007043.7 missense
Scores
3
11
5
Clinical Significance
Conservation
PhyloP100: 6.70
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.924
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KRR1 | NM_007043.7 | c.578T>C | p.Ile193Thr | missense_variant | 5/10 | ENST00000229214.9 | |
KRR1 | XM_047428133.1 | c.284T>C | p.Ile95Thr | missense_variant | 5/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KRR1 | ENST00000229214.9 | c.578T>C | p.Ile193Thr | missense_variant | 5/10 | 1 | NM_007043.7 | P1 | |
KRR1 | ENST00000438169.6 | c.578T>C | p.Ile193Thr | missense_variant | 5/9 | 1 | |||
KRR1 | ENST00000550023.5 | n.678T>C | non_coding_transcript_exon_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4AN: 1458806Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2AN XY: 725774
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
4
AN:
1458806
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
725774
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Bravo
AF:
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 | Sep 14, 2023 | The c.578T>C (p.I193T) alteration is located in exon 5 (coding exon 5) of the KRR1 gene. This alteration results from a T to C substitution at nucleotide position 578, causing the isoleucine (I) at amino acid position 193 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
B;.
Vest4
MutPred
Gain of disorder (P = 0.0205);Gain of disorder (P = 0.0205);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at