1-31577329-G-T

Position:

• chr1-31577329-G-T

Variant summary

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

The NM_022164.3(TINAGL1):​c.181G>T​(p.Asp61Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TINAGL1 NM_022164.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.42

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 (HGNC:):

ACMG classification

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	Protein	UniProt
TINAGL1	NM_022164.3	c.181G>T	p.Asp61Tyr	missense_variant	2/12	ENST00000271064.12	NP_071447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TINAGL1	ENST00000271064.12	c.181G>T	p.Asp61Tyr	missense_variant	2/12	1	NM_022164.3	ENSP00000271064.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2021

The c.181G>T (p.D61Y) alteration is located in exon 2 (coding exon 1) of the TINAGL1 gene. This alteration results from a G to T substitution at nucleotide position 181, causing the aspartic acid (D) at amino acid position 61 to be replaced by a tyrosine (Y). 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	0.15
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0070	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		0.93	.;P
Vest4		0.30
MutPred		0.48		Loss of disorder (P = 0.0956);Loss of disorder (P = 0.0956);
MVP		0.69
MPC		0.59
ClinPred		0.96	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.19
gMVP		0.82

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

Other links and lift over

dbSNP: rs540621515; hg19: chr1-32042930;