6-54321103-G-C

Variant names:

• chr6-54321103-G-C
• rs2297985
• NM_014464.4:c.420-194G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014464.4(TINAG):​c.420-194G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,244 control chromosomes in the GnomAD database, including 831 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.068 (831 hom., cov: 34)
• Consequence: TINAG NM_014464.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.512
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TINAG	NM_014464.4	c.420-194G>C		intron_variant	Intron 2 of 10	ENST00000259782.9	NP_055279.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TINAG	ENST00000259782.9	c.420-194G>C		intron_variant	Intron 2 of 10	1	NM_014464.4	ENSP00000259782.4
TINAG	ENST00000370869.7	c.408-194G>C		intron_variant	Intron 3 of 5	3		ENSP00000359906.3
TINAG	ENST00000370864.3	c.366-194G>C		intron_variant	Intron 2 of 3	2		ENSP00000359901.3
TINAG	ENST00000486436.1	n.482-194G>C		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0681 AC: 10359 AN: 152126 Hom.: 824 Cov.: 34

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.0422

Gnomad FIN AF: 0.0225

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0682 AC: 10384 AN: 152244 Hom.: 831 Cov.: 34 AF XY: 0.0693 AC XY: 5160 AN XY: 74434

African (AFR) AF: 0.164 AC: 6802 AN: 41534

American (AMR) AF: 0.0259 AC: 396 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.302 AC: 1565 AN: 5178

South Asian (SAS) AF: 0.0419 AC: 202 AN: 4826

European-Finnish (FIN) AF: 0.0225 AC: 239 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1052 AN: 68004

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

Alfa AF: 0.0432 Hom.: 56

Bravo AF: 0.0739

Asia WGS AF: 0.167 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2297985; hg19: chr6-54185901;