11-34456194-C-T

Position:

• chr11-34456194-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.19

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]

ACMG classification

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	Protein	UniProt
CAT	NM_001752.4	c.895C>T	p.Leu299Phe	missense_variant	7/13	ENST00000241052.5	NP_001743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAT	ENST00000241052.5	c.895C>T	p.Leu299Phe	missense_variant	7/13	1	NM_001752.4	ENSP00000241052	P1
CAT	ENST00000528104.2	n.265C>T		non_coding_transcript_exon_variant	2/3	2
CAT	ENST00000650153.1	c.*715C>T		3_prime_UTR_variant, NMD_transcript_variant	6/9			ENSP00000497751

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2023

The 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;