NM_001063.4:c.1570_1572delCTGinsTTA

Variant names:

• chr3-133768112-CTG-TTA
• NM_001063.4:c.1570_1572delCTGinsTTA
• TF p.525

GermlineCancer (beta)

Variant summary

Our verdict is Uncertain significance.

+1 Uncertain · Cold

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received 1 classification points (ACMG Germline Pathogenicity v2019). PM2BP7

The NM_001063.4(TF):c.1570_1572delCTGinsTTA (p.525) variant causes a synonymous change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TF NM_001063.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41
• 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, ClinGen, Orphanet, Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 1 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: AR) (threshold 0.001) — PM2 moderate.
	BP7Synonymous variant, no splicing impact		Synonymous variant at non-conserved position with no predicted splicing impact (BP7); Synonymous at non-conserved position, no splicing concern — benign (BP7).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_001063.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TF NM_001063.4	MANE Select	c.1570_1572delCTGinsTTA p.525	synonymous	N/A	Prot: NP_001054.2 UniProt:
	TF NM_001354703.2		c.1438_1440delCTGinsTTA p.481	synonymous	N/A	Prot: NP_001341632.2
	TF NM_001354704.2		c.1189_1191delCTGinsTTA p.398	synonymous	N/A	Prot: NP_001341633.2

TF NM_001063.4

MANE Select

HGVSc / HGVSpc.1570_1572delCTGinsTTAp.525

Exon rankN/A

synonymous

Prot: NP_001054.2UniProt: P02787Q06AH7A0PJA6

TF NM_001354703.2

HGVSc / HGVSpc.1438_1440delCTGinsTTAp.481

Exon rankN/A

synonymous

Prot: NP_001341632.2

TF NM_001354704.2

HGVSc / HGVSpc.1189_1191delCTGinsTTAp.398

Exon rankN/A

synonymous

Prot: NP_001341633.2

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	TF ENST00000402696.9	TSL:1MANE Select	c.1570_1572delCTGinsTTA p.525	synonymous	N/A	Prot: ENSP00000385834.3 UniProt:
	TF ENST00000877249.1		c.922_924delCTGinsTTA p.309	synonymous	N/A	Prot: ENSP00000547308.1 UniProt:
	TF ENST00000877246.1		c.583_585delCTGinsTTA p.196	synonymous	N/A	Prot: ENSP00000547305.1 UniProt:

TF ENST00000402696.9

TSL:1MANE Select

HGVSc / HGVSpc.1570_1572delCTGinsTTAp.525

Exon rankN/A

synonymous

Prot: ENSP00000385834.3UniProt: P02787

TF ENST00000877249.1

HGVSc / HGVSpc.922_924delCTGinsTTAp.309

Exon rankN/A

synonymous

Prot: ENSP00000547308.1UniProt: A0ACI8QAC3

TF ENST00000877246.1

HGVSc / HGVSpc.583_585delCTGinsTTAp.196

Exon rankN/A

synonymous

Prot: ENSP00000547305.1UniProt: A0ACI8R955

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	2.4

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

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.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr3-133486956;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar