3-46439378-T-C
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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):āc.1826A>Gā(p.His609Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,461,878 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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000021 ( 0 hom. )
Consequence
LTF
NM_002343.6 missense
NM_002343.6 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 5.02
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, 0.884
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LTF | NM_002343.6 | c.1826A>G | p.His609Arg | missense_variant | 15/17 | ENST00000231751.9 | NP_002334.2 | |
LTF | NM_001321121.2 | c.1820A>G | p.His607Arg | missense_variant | 15/17 | NP_001308050.1 | ||
LTF | NM_001321122.2 | c.1787A>G | p.His596Arg | missense_variant | 18/20 | NP_001308051.1 | ||
LTF | NM_001199149.2 | c.1694A>G | p.His565Arg | missense_variant | 15/17 | NP_001186078.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LTF | ENST00000231751.9 | c.1826A>G | p.His609Arg | missense_variant | 15/17 | 1 | NM_002343.6 | ENSP00000231751 | P3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.000103 AC: 26AN: 251360Hom.: 0 AF XY: 0.000110 AC XY: 15AN XY: 135836
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461878Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 727238
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GnomAD4 genome Cov.: 33
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33
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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 | Feb 27, 2024 | The c.1826A>G (p.H609R) alteration is located in exon 15 (coding exon 15) of the LTF gene. This alteration results from a A to G substitution at nucleotide position 1826, causing the histidine (H) at amino acid position 609 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;.;P;D
Vest4
MutPred
Gain of MoRF binding (P = 0.0307);.;.;.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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