chr11-34456194-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001752.4(CAT):​c.895C>T​(p.Leu299Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: 32)

Consequence

CAT
NM_001752.4 missense

Scores

5
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.19
Variant links:
Genes affected
CAT (HGNC:1516): (catalase) This gene encodes catalase, a key antioxidant enzyme in the bodies defense against oxidative stress. Catalase is a heme enzyme that is present in the peroxisome of nearly all aerobic cells. Catalase converts the reactive oxygen species hydrogen peroxide to water and oxygen and thereby mitigates the toxic effects of hydrogen peroxide. Oxidative stress is hypothesized to play a role in the development of many chronic or late-onset diseases such as diabetes, asthma, Alzheimer's disease, systemic lupus erythematosus, rheumatoid arthritis, and cancers. Polymorphisms in this gene have been associated with decreases in catalase activity but, to date, acatalasemia is the only disease known to be caused by this gene. [provided by RefSeq, Oct 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CATNM_001752.4 linkuse as main transcriptc.895C>T p.Leu299Phe missense_variant 7/13 ENST00000241052.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CATENST00000241052.5 linkuse as main transcriptc.895C>T p.Leu299Phe missense_variant 7/131 NM_001752.4 P1
CATENST00000528104.2 linkuse as main transcriptn.265C>T non_coding_transcript_exon_variant 2/32
CATENST00000650153.1 linkuse as main transcriptc.*715C>T 3_prime_UTR_variant, NMD_transcript_variant 6/9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 24, 2023The c.895C>T (p.L299F) alteration is located in exon 7 (coding exon 7) of the CAT gene. This alteration results from a C to T substitution at nucleotide position 895, causing the leucine (L) at amino acid position 299 to be replaced by a phenylalanine (F). 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
0.94
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Benign
-0.16
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.89
D;D
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.73
FATHMM_MKL
Benign
0.35
N
LIST_S2
Uncertain
0.97
.;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.82
D;D
MetaSVM
Uncertain
0.79
D
MutationAssessor
Pathogenic
4.4
H;H
MutationTaster
Benign
0.98
D
PrimateAI
Benign
0.39
T
PROVEAN
Uncertain
-3.2
D;.
REVEL
Uncertain
0.53
Sift
Uncertain
0.0020
D;.
Sift4G
Pathogenic
0.0010
D;.
Polyphen
0.85
P;P
Vest4
0.58
MutPred
0.75
Gain of methylation at K301 (P = 0.1013);Gain of methylation at K301 (P = 0.1013);
MVP
0.94
MPC
0.42
ClinPred
0.98
D
GERP RS
-7.6
Varity_R
0.54
gMVP
0.82

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.

Other links and lift over

hg19: chr11-34477741; API