Variant 3-46439378-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002343.6(LTF):c.1826A>G(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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

LTF
NM_002343.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.02

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 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
LTF	NM_002343.6 linkuse as main transcript	c.1826A>G	p.His609Arg	missense_variant	15/17	ENST00000231751.9
LTF	NM_001321121.2 linkuse as main transcript	c.1820A>G	p.His607Arg	missense_variant	15/17
LTF	NM_001321122.2 linkuse as main transcript	c.1787A>G	p.His596Arg	missense_variant	18/20
LTF	NM_001199149.2 linkuse as main transcript	c.1694A>G	p.His565Arg	missense_variant	15/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTF	ENST00000231751.9 linkuse as main transcript	c.1826A>G	p.His609Arg	missense_variant	15/17	1	NM_002343.6	P3	P02788-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000103

AC:

AN:

251360

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000824

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.33

T;.;.;.

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Pathogenic

0.88

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.2

M;.;.;.

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-6.6

D;D;D;D

REVEL

Benign

0.21

Sift

Uncertain

0.017

D;D;D;D

Sift4G

Uncertain

0.046

D;D;D;D

Polyphen

0.62

P;.;P;D

Vest4

0.55

MutPred

0.89

Gain of MoRF binding (P = 0.0307);.;.;.;

MVP

0.55

MPC

0.12

ClinPred

0.69

GERP RS

4.0

Varity_R

0.80

gMVP

0.85

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over