Variant 1-31577281-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000271064.12(TINAGL1):c.133G>A(p.Gly45Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,612,544 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

TINAGL1
ENST00000271064.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.24

Variant links:

Genes affected

TINAGL1 (HGNC:19168): (tubulointerstitial nephritis antigen like 1) The protein encoded by this gene is similar in sequence to tubulointerstitial nephritis antigen, a secreted glycoprotein that is recognized by antibodies in some types of immune-related tubulointerstitial nephritis. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

TINAGL1 links:

LOC105378626 (HGNC:):

LOC105378626 links:

Genome browser will be placed here

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, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TINAGL1	NM_022164.3 linkuse as main transcript	c.133G>A	p.Gly45Ser	missense_variant	2/12	ENST00000271064.12	NP_071447.1
LOC105378626	XR_007065603.1 linkuse as main transcript	n.1700+563C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TINAGL1	ENST00000271064.12 linkuse as main transcript	c.133G>A	p.Gly45Ser	missense_variant	2/12	1	NM_022164.3	ENSP00000271064	P1	Q9GZM7-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000203

AC:

AN:

246354

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

133830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000455

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1460298

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726506

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000621

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000676

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

Sep 22, 2022

The c.133G>A (p.G45S) alteration is located in exon 2 (coding exon 1) of the TINAGL1 gene. This alteration results from a G to A substitution at nucleotide position 133, causing the glycine (G) at amino acid position 45 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

0.14

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.056

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.8

M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-3.1

D;D

REVEL

Uncertain

0.32

Sift

Benign

0.050

D;D

Sift4G

Uncertain

0.058

T;T

Polyphen

1.0

.;D

Vest4

0.71

MutPred

0.56

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);

MVP

0.72

MPC

1.4

ClinPred

0.95

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.44

gMVP

0.92

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