Variant 4-112278233-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_052864.3(TIFA):c.184G>A(p.Asp62Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TIFA
NM_052864.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11

Variant links:

Genes affected

TIFA (HGNC:19075): (TRAF interacting protein with forkhead associated domain) This gene encodes an adapter protein involved in adaptive and innate immunity. This protein includes a forkhead-associated (FHA) domain that specifically binds to phosphorylated serine and threonine residues. In response to bacterial infection, the encoded host cell protein undergoes an intermolecular interaction between the FHA domain and a phosphorylated threonine that leads to protein oligomerization and stimulation of the NF-kappa B and other downstream signaling pathways. This protein exhibits reduced expression in hepatocellular carcinoma and may suppress hepatocellular carcinoma progression. This protein may also play a role in the DNA damage response. [provided by RefSeq, Jun 2018]

TIFA links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIFA	NM_052864.3 linkuse as main transcript	c.184G>A	p.Asp62Asn	missense_variant	2/2	ENST00000361717.4	NP_443096.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TIFA	ENST00000361717.4 linkuse as main transcript	c.184G>A	p.Asp62Asn	missense_variant	2/2	1	NM_052864.3	ENSP00000354911	P1
TIFA	ENST00000500655.2 linkuse as main transcript	c.184G>A	p.Asp62Asn	missense_variant	2/2	3		ENSP00000424231	P1
TIFA	ENST00000610220.2 linkuse as main transcript	c.184G>A	p.Asp62Asn	missense_variant	2/2			ENSP00000516322	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249718

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.184G>A (p.D62N) alteration is located in exon 2 (coding exon 1) of the TIFA gene. This alteration results from a G to A substitution at nucleotide position 184, causing the aspartic acid (D) at amino acid position 62 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.63

D;D

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.020

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.28

Sift

Benign

0.084

T;T

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.63

MutPred

0.67

Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);

MVP

0.74

MPC

1.1

ClinPred

0.83

GERP RS

5.9

Varity_R

0.43

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over