Variant 6-54321358-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014464.4(TINAG):c.481A>G(p.Ile161Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TINAG
NM_014464.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

TINAG (HGNC:14599): (tubulointerstitial nephritis antigen) This gene encodes a glycoprotein that is restricted within the kidney to the basement membranes underlying the epithelium of Bowman's capsule and proximal and distal tubules. Autoantibodies against this protein are found in sera of patients with tubulointerstital nephritis, membranous nephropathy and anti-glomerular basement membrane nephritis. Ontogeny studies suggest that the expression of this antigen is developmentally regulated in a precise spatial and temporal pattern throughout nephrogenesis. [provided by RefSeq, Nov 2011]

TINAG links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TINAG	NM_014464.4 linkuse as main transcript	c.481A>G	p.Ile161Val	missense_variant	3/11	ENST00000259782.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TINAG	ENST00000259782.9 linkuse as main transcript	c.481A>G	p.Ile161Val	missense_variant	3/11	1	NM_014464.4	P1	Q9UJW2-1
TINAG	ENST00000370869.7 linkuse as main transcript	c.469A>G	p.Ile157Val	missense_variant	4/6	3
TINAG	ENST00000370864.3 linkuse as main transcript	c.427A>G	p.Ile143Val	missense_variant	3/4	2
TINAG	ENST00000486436.1 linkuse as main transcript	n.543A>G		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726912

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 29, 2022

The c.481A>G (p.I161V) alteration is located in exon 3 (coding exon 3) of the TINAG gene. This alteration results from a A to G substitution at nucleotide position 481, causing the isoleucine (I) at amino acid position 161 to be replaced by a valine (V). 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

Benign

0.098

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.29

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.050

D;D;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.99

.;D;.

Vest4

0.44

MutPred

0.49

.;Gain of catalytic residue at I161 (P = 0.0032);.;

MVP

0.18

MPC

0.055

ClinPred

0.89

GERP RS

3.3

Varity_R

0.088

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.30

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.30

Position offset: 28

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