Variant chr3-46459723-T-A details in Genebe, Genetics Data Aggregator

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

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]

LTF links:

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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
LTF	NM_002343.6 linkuse as main transcript	c.140A>T	p.Lys47Ile	missense_variant	2/17	ENST00000231751.9
LTF	NM_001321121.2 linkuse as main transcript	c.140A>T	p.Lys47Ile	missense_variant	2/17
LTF	NM_001321122.2 linkuse as main transcript	c.101A>T	p.Lys34Ile	missense_variant	5/20
LTF	NM_001199149.2 linkuse as main transcript	c.8A>T	p.Lys3Ile	missense_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9 linkuse as main transcript	c.140A>T	p.Lys47Ile	missense_variant	2/17	1	NM_002343.6	P3	P02788-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1425596

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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.:

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

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

LIST_S2

Benign

0.34

T;T;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.9

M;.;.;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.29

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over