rs1126478

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002343.6(LTF):​c.140A>T​(p.Lys47Ile) 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 benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K47R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LTF
NM_002343.6 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10411322).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LTFNM_002343.6 linkuse as main transcriptc.140A>T p.Lys47Ile missense_variant 2/17 ENST00000231751.9
LTFNM_001321121.2 linkuse as main transcriptc.140A>T p.Lys47Ile missense_variant 2/17
LTFNM_001321122.2 linkuse as main transcriptc.101A>T p.Lys34Ile missense_variant 5/20
LTFNM_001199149.2 linkuse as main transcriptc.8A>T p.Lys3Ile missense_variant 2/17

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LTFENST00000231751.9 linkuse as main transcriptc.140A>T p.Lys47Ile missense_variant 2/171 NM_002343.6 P3P02788-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1425596
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
708508
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
2.3
DANN
Benign
0.89
DEOGEN2
Benign
0.22
T;.;.;.;.
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.34
T;T;T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.10
T;T;T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Uncertain
2.9
M;.;.;.;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-4.6
D;D;D;D;D
REVEL
Benign
0.098
Sift
Uncertain
0.018
D;D;D;D;D
Sift4G
Benign
0.073
T;D;T;T;T
Polyphen
0.037
B;.;B;B;.
Vest4
0.23
MutPred
0.46
Loss of disorder (P = 0.014);.;Loss of disorder (P = 0.014);.;.;
MVP
0.26
MPC
0.12
ClinPred
0.30
T
GERP RS
-9.7
Varity_R
0.38
gMVP
0.65

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1126478; hg19: chr3-46501213; API