NM_002343.6:c.2066G>C

Variant names:

• chr3-46437972-C-G
• rs1702424552
• NM_002343.6:c.2066G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002343.6(LTF):​c.2066G>C​(p.Gly689Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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. G689D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTF NM_002343.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038743764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTF	NM_002343.6	c.2066G>C	p.Gly689Ala	missense_variant	Exon 16 of 17	ENST00000231751.9	NP_002334.2
LTF	NM_001321121.2	c.2060G>C	p.Gly687Ala	missense_variant	Exon 16 of 17		NP_001308050.1
LTF	NM_001321122.2	c.2027G>C	p.Gly676Ala	missense_variant	Exon 19 of 20		NP_001308051.1
LTF	NM_001199149.2	c.1934G>C	p.Gly645Ala	missense_variant	Exon 16 of 17		NP_001186078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTF	ENST00000231751.9	c.2066G>C	p.Gly689Ala	missense_variant	Exon 16 of 17	1	NM_002343.6	ENSP00000231751.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.6
DANN	Benign	0.059
DEOGEN2	Benign	0.035	T;.;.;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0037	N
LIST_S2	Benign	0.12	T;T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.039	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-4.0	N;.;.;.
PhyloP100		3.9
PrimateAI	Benign	0.41	T
PROVEAN	Benign	2.8	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.0	B;.;B;B
Vest4		0.079
MutPred		0.56		Loss of ubiquitination at K694 (P = 0.1037);.;.;.;
MVP		0.18
MPC		0.073
ClinPred		0.041	T
GERP RS		3.3
Varity_R		0.055
gMVP		0.24
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs1702424552; hg19: chr3-46479463;