3-133746447-CTC-TTG

Variant names:

• chr3-133746447-CTC-TTG
• NM_001063.4:c.7_9delCTCinsTTG
• TF p.4

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP7

The NM_001063.4(TF):​c.7_9delCTCinsTTG​(p.4) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L3L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TF NM_001063.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 0 publications found

Genes affected

TF (HGNC:11740): (transferrin) This gene encodes a glycoprotein with an approximate molecular weight of 76.5 kDa. It is thought to have been created as a result of an ancient gene duplication event that led to generation of homologous C and N-terminal domains each of which binds one ion of ferric iron. The function of this protein is to transport iron from the intestine, reticuloendothelial system, and liver parenchymal cells to all proliferating cells in the body. This protein may also have a physiologic role as granulocyte/pollen-binding protein (GPBP) involved in the removal of certain organic matter and allergens from serum. [provided by RefSeq, Sep 2009]

TF Gene-Disease associations (from GenCC):

• atransferrinemia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp

ENSG00000291042 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP7: Synonymous conserved (PhyloP=0.82 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001063.4. 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
	TF	NM_001063.4	MANE Select	c.7_9delCTCinsTTG	p.4	synonymous	N/A	NP_001054.2	P02787
	TF	NM_001354704.2		c.-202_-200delCTCinsTTG		5_prime_UTR	Exon 1 of 16	NP_001341633.2
	TF	NM_001354703.2		c.-89-1965_-89-1963delCTCinsTTG		intron	N/A	NP_001341632.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TF	ENST00000402696.9	TSL:1 MANE Select	c.7_9delCTCinsTTG	p.4	synonymous	N/A	ENSP00000385834.3	P02787
	TF	ENST00000877249.1		c.7_9delCTCinsTTG	p.4	synonymous	N/A	ENSP00000547308.1
	TF	ENST00000877246.1		c.7_9delCTCinsTTG	p.4	synonymous	N/A	ENSP00000547305.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.82

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-133465291;