Variant 1-31577270-G-A 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_022164.3(TINAGL1):c.122G>A(p.Arg41Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000138 in 1,611,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

TINAGL1
NM_022164.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.01

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:

TINAGL1 (HGNC:):

TINAGL1 links:

Genome browser will be placed here

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=0.16503274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TINAGL1	NM_022164.3 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	2/12	ENST00000271064.12	NP_071447.1	Q9GZM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TINAGL1	ENST00000271064.12 linkuse as main transcript	c.122G>A	p.Arg41Gln	missense_variant	2/12	1	NM_022164.3	ENSP00000271064.7		Q9GZM7-1

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000196

AC:

AN:

244744

Hom.:

AF XY:

0.000173

AC XY:

AN XY:

133106

show subpopulations

Gnomad AFR exome

AF:

0.0000634

Gnomad AMR exome

AF:

0.000407

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000496

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000128

AC:

187

AN:

1459544

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000909

Gnomad4 OTH exome

AF:

0.000448

GnomAD4 genome

AF:

0.000230

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000293

Hom.:

Bravo

AF:

0.000249

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

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 30, 2021

The c.122G>A (p.R41Q) 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 122, causing the arginine (R) at amino acid position 41 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.024

.;T

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.69

MutationAssessor

Benign

2.0

M;M

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.23

Sift

Benign

0.34

T;T

Sift4G

Benign

0.60

T;T

Polyphen

1.0

.;D

Vest4

0.46

MVP

0.65

MPC

1.4

ClinPred

0.12

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.12

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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