rs10662431

Variant names:

• chr3-46459794-C-CCTA
• rs10662431
• NM_002343.6:c.68_69insTAG

Your query was ambiguous. Multiple possible variants found:

• chr3-46459794-C-CCTA
• chr3-46459794-C-CCTT

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_002343.6(LTF):​c.68_69insTAG​(p.Arg22_Arg23insSer) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000113 in 1,412,388 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: LTF NM_002343.6 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 21 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_002343.6. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002343.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	NM_002343.6	MANE Select	c.68_69insTAG	p.Arg22_Arg23insSer	disruptive_inframe_insertion	Exon 2 of 17	NP_002334.2	P02788-1
	LTF	NM_001321121.2		c.68_69insTAG	p.Arg22_Arg23insSer	disruptive_inframe_insertion	Exon 2 of 17	NP_001308050.1	E7ER44
	LTF	NM_001321122.2		c.29_30insTAG	p.Arg9_Arg10insSer	disruptive_inframe_insertion	Exon 5 of 20	NP_001308051.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTF	ENST00000231751.9	TSL:1 MANE Select	c.68_69insTAG	p.Arg22_Arg23insSer	disruptive_inframe_insertion	Exon 2 of 17	ENSP00000231751.4	P02788-1
	LTF	ENST00000417439.5	TSL:1	c.68_69insTAG	p.Arg22_Arg23insSer	disruptive_inframe_insertion	Exon 2 of 17	ENSP00000405546.1	E7ER44
	LTF	ENST00000947212.1		c.68_69insTAG	p.Arg22_Arg23insSer	disruptive_inframe_insertion	Exon 2 of 18	ENSP00000617271.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD2 exomes AF: 0.00000484 AC: 1 AN: 206520 AF XY: 0.00000885

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 16 AN: 1412388 Hom.: 0 Cov.: 36 AF XY: 0.0000142 AC XY: 10 AN XY: 701768

African (AFR) AF: 0.00 AC: 0 AN: 29030

American (AMR) AF: 0.00 AC: 0 AN: 35574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24956

East Asian (EAS) AF: 0.00 AC: 0 AN: 34662

South Asian (SAS) AF: 0.00 AC: 0 AN: 78586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5312

European-Non Finnish (NFE) AF: 0.0000146 AC: 16 AN: 1093084

Other (OTH) AF: 0.00 AC: 0 AN: 58266

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs10662431; hg19: chr3-46501284;