3-46445289-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002343.6(LTF):c.1505G>A(p.Cys502Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000747 in 1,606,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
LTF
NM_002343.6 missense
NM_002343.6 missense
Scores
10
5
4
Clinical Significance
Conservation
PhyloP100: 6.90
Genes affected
LTF (HGNC:6720): (lactotransferrin) This gene is a member of the transferrin family of genes and its protein product is found in the secondary granules of neutrophils. The protein is a major iron-binding protein in milk and body secretions with an antimicrobial activity, making it an important component of the non-specific immune system. The protein demonstrates a broad spectrum of properties, including regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. Antimicrobial, antiviral, antifungal and antiparasitic activity has been found for this protein and its peptides. Activity against both DNA and RNA viruses has been found, including activity against SARS-CoV-2, and HIV. [provided by RefSeq, Jul 2021]
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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, 0.866
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LTF | NM_002343.6 | c.1505G>A | p.Cys502Tyr | missense_variant | 12/17 | ENST00000231751.9 | NP_002334.2 | |
LTF | NM_001321121.2 | c.1499G>A | p.Cys500Tyr | missense_variant | 12/17 | NP_001308050.1 | ||
LTF | NM_001321122.2 | c.1466G>A | p.Cys489Tyr | missense_variant | 15/20 | NP_001308051.1 | ||
LTF | NM_001199149.2 | c.1373G>A | p.Cys458Tyr | missense_variant | 12/17 | NP_001186078.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LTF | ENST00000231751.9 | c.1505G>A | p.Cys502Tyr | missense_variant | 12/17 | 1 | NM_002343.6 | ENSP00000231751 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000413 AC: 6AN: 1454462Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4AN XY: 723218
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74368
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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 | Jul 13, 2022 | The c.1505G>A (p.C502Y) alteration is located in exon 12 (coding exon 12) of the LTF gene. This alteration results from a G to A substitution at nucleotide position 1505, causing the cysteine (C) at amino acid position 502 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;D
Sift4G
Pathogenic
D;D;D;D
Polyphen
D;.;D;D
Vest4
MutPred
Gain of glycosylation at Y507 (P = 0.0346);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at