Genetic Variant NM_001063.4:c.739C>A (chr3-133756878-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001063.4(TF):c.739C>A(p.Leu247Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Synonymous variant affecting the same amino acid position (i.e. L247L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

TF
NM_001063.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.268

Publications

65 publications found

Variant links:

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

TF links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17288837).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TF	NM_001063.4	MANE Select	c.739C>A	p.Leu247Met	missense	Exon 7 of 17	NP_001054.2	P02787
TF	NM_001354703.2		c.607C>A	p.Leu203Met	missense	Exon 13 of 23	NP_001341632.2
TF	NM_001354704.2		c.358C>A	p.Leu120Met	missense	Exon 6 of 16	NP_001341633.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TF	ENST00000402696.9	TSL:1 MANE Select	c.739C>A	p.Leu247Met	missense	Exon 7 of 17	ENSP00000385834.3	P02787
TF	ENST00000877249.1		c.91C>A	p.Leu31Met	missense	Exon 2 of 12	ENSP00000547308.1
TF	ENST00000482271.5	TSL:4	c.358C>A	p.Leu120Met	missense	Exon 6 of 6	ENSP00000419338.1	C9JVG0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.21

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.045

M_CAP

Benign

0.0093

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

PhyloP100

-0.27

PrimateAI

Benign

0.23

PROVEAN

Benign

0.11

REVEL

Benign

0.049

Sift

Benign

0.11

Sift4G

Benign

0.12

Polyphen

0.048

Vest4

0.26

MutPred

0.46

Gain of phosphorylation at T250 (P = 0.136)

MVP

0.16

MPC

0.36

ClinPred

0.091

GERP RS

-0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.26

gMVP

0.34

Mutation Taster

=70/30

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over