Variant 6-54326914-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014464.4(TINAG):c.622A>T(p.Thr208Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TINAG
NM_014464.4 missense, splice_region

Scores

Splicing: ADA: 0.1230

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.09

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1299232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TINAG	NM_014464.4 linkuse as main transcript	c.622A>T	p.Thr208Ser	missense_variant, splice_region_variant	4/11	ENST00000259782.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TINAG	ENST00000259782.9 linkuse as main transcript	c.622A>T	p.Thr208Ser	missense_variant, splice_region_variant	4/11	1	NM_014464.4	P1	Q9UJW2-1
TINAG	ENST00000370864.3 linkuse as main transcript	c.568A>T	p.Thr190Ser	missense_variant	4/4	2
TINAG	ENST00000370869.7 linkuse as main transcript	c.610A>T	p.Thr204Ser	missense_variant, splice_region_variant	5/6	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460818

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726618

show subpopulations

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:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Feb 17, 2024

The c.622A>T (p.T208S) alteration is located in exon 4 (coding exon 4) of the TINAG gene. This alteration results from a A to T substitution at nucleotide position 622, causing the threonine (T) at amino acid position 208 to be replaced by a serine (S). 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

0.082

BayesDel_addAF

Benign

0.0031

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

-0.084

Eigen_PC

Benign

0.023

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.29

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.88

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.067

Sift

Uncertain

0.025

D;T;T

Sift4G

Benign

0.066

T;T;T

Polyphen

0.55

.;P;.

Vest4

0.25

MutPred

0.27

.;Gain of disorder (P = 0.0416);.;

MVP

0.31

MPC

0.010

ClinPred

0.31

GERP RS

4.5

Varity_R

0.063

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.12

dbscSNV1_RF

Benign

0.32

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.24

Position offset: -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