chr6-54320610-G-C

Position:

• chr6-54320610-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014464.4(TINAG):​c.387G>C​(p.Glu129Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TINAG NM_014464.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.12

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]

ACMG classification

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=0.19110596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TINAG	NM_014464.4	c.387G>C	p.Glu129Asp	missense_variant	2/11	ENST00000259782.9	NP_055279.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TINAG	ENST00000259782.9	c.387G>C	p.Glu129Asp	missense_variant	2/11	1	NM_014464.4	ENSP00000259782.4
TINAG	ENST00000370869.7	c.375G>C	p.Glu125Asp	missense_variant	3/6	3		ENSP00000359906.3
TINAG	ENST00000370864.3	c.333G>C	p.Glu111Asp	missense_variant	2/4	2		ENSP00000359901.3
TINAG	ENST00000486436.1	n.449G>C		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Jul 09, 2024

The c.387G>C (p.E129D) alteration is located in exon 2 (coding exon 2) of the TINAG gene. This alteration results from a G to C substitution at nucleotide position 387, causing the glutamic acid (E) at amino acid position 129 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.093
Sift	Benign	0.33	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.70	.;P;.
Vest4		0.43
MutPred		0.28		.;Gain of helix (P = 0.0425);.;
MVP		0.40
MPC		0.0092
ClinPred		0.72	D
GERP RS		3.1
Varity_R		0.073
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-54185408;